2021 |
Feng YC, Zhao XH, Teng L, Thorne RF, Jin L, Zhang XD, 'The pan-cancer lncRNA MILIP links c-Myc to p53 repression', Molecular and Cellular Oncology, 8 (2021)
We have recently identified the MYC proto-oncogene, bHLH transcription factor (MYC, best known as c-Myc)-responsive pan-cancer lncRNA c-Myc-Inducible Long noncoding RNA Inactivati... [more]
We have recently identified the MYC proto-oncogene, bHLH transcription factor (MYC, best known as c-Myc)-responsive pan-cancer lncRNA c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP) as an oncogenic driver. Our studies show that MILIP facilitates tumor protein p53 (TP53, best known as p53) turnover by reducing its SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2), thus promoting cell survival, proliferation, and tumorigenicity. MILIP may thus represent an anti-cancer target for counteracting the c-Myc axis.
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2021 |
Wang R, Cao L, Thorne RF, Zhang XD, Li J, Shao F, et al., 'LncRNA GIRGL drives CAPRIN1-mediated phase separation to suppress glutaminase-1 translation under glutamine deprivation.', Sci Adv, 7 (2021) [C1]
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2021 |
Guo AJ, Wang FJ, Ji Q, Geng HW, Yan X, Wang LQ, et al., 'Proteome Analyses Reveal S100A11, S100P, and RBM25 Are Tumor Biomarkers in Colorectal Cancer', Proteomics - Clinical Applications, 15 (2021)
Purpose: The prognosis for colorectal cancer (CRC) patients is drastically impacted by the presence of lymph node or liver metastases at diagnosis or resection. On this basis it i... [more]
Purpose: The prognosis for colorectal cancer (CRC) patients is drastically impacted by the presence of lymph node or liver metastases at diagnosis or resection. On this basis it is sought to identify novel proteins as biomarkers and determinants of CRC metastasis. Experimental Design: Proteomic analyses are undertaken using primary tissues from ten Chinese CRC patients presenting with or without liver metastases and immunohistochemistry used to validate selected proteins in an independent patient cohort. Results: Comparing CRC against paired normal adjacent tissues identifies 1559 differentially expressed proteins (DEPs) with 974 upregulated and 585 downregulated proteins, respectively. The highest number of DEPs is selectively associated with metastatic tumors (519 upregulated and 267 downregulated proteins, respectively) with a smaller number of unique DEPs identified only in non-metastatic CRC cases (116 upregulated and 29 downregulated proteins, respectively). The remaining DEPs are commonly expressed in both non-metastatic and metastatic tumors. The upregulation of three representative DEPs (S100A11, S100P, and RBM25) is confirmed using immunohistochemistry against 154 CRC tissues embedded in a tissue microarray. Conclusions and Clinical Relevance: The data reveal both previously identified CRC biomarkers along with novel candidates which provide a ready resource of DEPs in CRC for further investigation.
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2021 |
Li M, Thorne RF, Shi R, Zhang XD, Li J, Li J, et al., 'DDIT3 Directs a Dual Mechanism to Balance Glycolysis and Oxidative Phosphorylation during Glutamine Deprivation', Advanced Science, (2021)
Extracellular glutamine represents an important energy source for many cancer cells and its metabolism is intimately involved in maintaining redox homeostasis. The heightened meta... [more]
Extracellular glutamine represents an important energy source for many cancer cells and its metabolism is intimately involved in maintaining redox homeostasis. The heightened metabolic activity within tumor tissues can result in glutamine deficiency, necessitating metabolic reprogramming responses. Here, dual mechanisms involving the stress-responsive transcription factor DDIT3 (DNA damage induced transcript 3) that establishes an interrelationship between glycolysis and mitochondrial respiration are revealed. DDIT3 is induced during glutamine deprivation to promote glycolysis and adenosine triphosphate production via suppression of the negative glycolytic regulator TIGAR. In concert, a proportion of the DDIT3 pool translocates to the mitochondria and suppresses oxidative phosphorylation through LONP1-mediated down-regulation of COQ9 and COX4. This in turn dampens the sustained levels of reactive oxygen species that follow glutamine withdrawal. Together these mechanisms constitute an adaptive survival mechanism permitting tumor cells to survive metabolic stress induced by glutamine starvation.
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2021 |
Zhang C, Shen L, Zhu Y, Xu R, Deng Z, Liu X, et al., 'KDM6A promotes imatinib resistance through YY1-mediated transcriptional upregulation of TRKA independently of its demethylase activity in chronic myelogenous leukemia', THERANOSTICS, 11 2691-2705 (2021) [C1]
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2020 |
Gao S, Liu G, Li J, Chen J, Li L, Li Z, et al., 'Antimicrobial Activity of Lemongrass Essential Oil (Cymbopogon flexuosus) and Its Active Component Citral Against Dual-Species Biofilms of Staphylococcus aureus and Candida Species', FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 10 (2020)
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2020 |
Chen S, Thorne RF, Zhang XD, Wu M, Liu L, 'Non-coding RNAs, guardians of the p53 galaxy', Seminars in Cancer Biology, (2020)
The TP53 gene is arguably the most important tumor suppressor gene known, contributing multifaceted roles to the process of tumor development. Its protein product p53, is a crucia... [more]
The TP53 gene is arguably the most important tumor suppressor gene known, contributing multifaceted roles to the process of tumor development. Its protein product p53, is a crucial sequence-specific transcription factor which regulates the expression of a large network of protein-coding genes, as well as thousands of noncoding RNAs (ncRNAs), notably microRNAs and long ncRNAs (lncRNAs). Through a variety of direct and indirect mechanisms, ncRNAs in turn modulate p53 levels and activity. Here the numbers of studies are steadily building which link the contributions of dysregulated ncRNAs to tumorigenesis via their participation throughout the p53 regulatory network. In this review, we will examine how the principal forms of ncRNAs, namely microRNAs, lncRNAs and circular RNAs (circRNAs) function as either effectors or regulators amongst the diversity of p53's cellular responses. We first discuss the more recently discovered connections between miRNAs and p53 signaling before focusing on the remarkable diversity of crosstalk evident between lncRNAs and p53, and subsequently, developing reports linking circRNAs to p53. Highlighted throughout the review are the mechanistic impacts of dysregulated ncRNAs on p53 functions as well as the possible prognostic implications of these interactions. We also describe the emerging connections between ncRNAs and the often-perplexing functions of mutant p53. Finally, in the context of p53 therapeutic approaches, we describe some of the challenges in ncRNA research and their potential for translation.
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2020 |
Sun X, Thorne RF, Zhang XD, He M, Li J, Feng S, et al., 'LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1a-FOXO4-p21-dependent signaling axis', EMBO Reports, 21 (2020) [C1]
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2020 |
Feng YC, Liu XY, Teng L, Ji Q, Wu Y, Li JM, et al., 'c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis', Nature Communications, 11 (2020) [C1]
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2020 |
Liu G, Zhao Y, Chen H, Jia J, Cheng X, Wang F, et al., 'Analysis of differentially expressed genes in a Chinese cohort of esophageal squamous cell carcinoma', Journal of Cancer, 11 3783-3793 (2020)
Esophageal squamous cell carcinoma (ESCC) is a leading malignancy in China with both high incidence and mortality. Towards improving outcomes, clinically-relevant biomarkers are u... [more]
Esophageal squamous cell carcinoma (ESCC) is a leading malignancy in China with both high incidence and mortality. Towards improving outcomes, clinically-relevant biomarkers are urgently needed for use as prognostic and treatment targets. Herein we applied RNA-seq for deep sequencing of ten matched pairs of ESCC and adjacent non-cancerous tissues (NT) from Chinese patients. Transcriptomic data mapped to approximately 64% of all annotated genes with 2,047 and 708 unigenes being differentially up-regulated and down-regulated, respectively, between ESCCs and NT samples (p<0.05). Dividing cases by pathological grade revealed significant differentially expressed genes (DEG) between ESCC and NT in both low and high differentiation cases (p<0.05) whereas gene expression differences were not significantly different between high and low differentiation ESCC tissues (p=0.053). Moreover, the majority of ESCC and NT tissues formed clusters in principal component analyses. The veracity of the DEG list was validated in a larger cohort of 45 patient samples, with down-regulated CLIC3, up-regulated CLIC4 and unchanged expression of CLIC2 confirmed in ESCC using quantitative PCR and Western blotting. Our data reveal both previously identified ESCC biomarkers along with novel candidates and represent a ready resource of DEGs in ESCC for further investigation.
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2020 |
Xu CL, Sang B, Liu GZ, Li JM, Zhang XD, Liu LX, et al., 'SENEBLOC, a long non-coding RNA suppresses senescence via p53-dependent and independent mechanisms', Nucleic Acids Research, 48 3089-3102 (2020) [C1]
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2020 |
Thorne RF, Wang Y, Zhang Y, Jing X, Zhang XD, de Bock CE, Oliveira CS, 'Evaluating nuclear translocation of surface receptors: recommendations arising from analysis of CD44', Histochemistry and Cell Biology, 153 77-87 (2020) [C1]
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2020 |
Liu X, Feng S, Zhang XD, Li J, Zhang K, Wu M, Thorne RF, 'Non-coding RNAs, metabolic stress and adaptive mechanisms in cancer.', Cancer Letters, 491 60-69 (2020) [C1]
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2020 |
La T, Jin L, Liu XY, Song ZH, Farrelly M, Feng YC, et al., 'Cylindromatosis is required for survival of a subset of melanoma cells.', Oncology Research, 28 385-398 (2020) [C1]
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2019 |
Nagarajan K, Soundarapandian K, Thorne RF, Li D, Li D, 'Activation of Pyroptotic Cell Death Pathways in Cancer: An Alternative Therapeutic Approach', Translational Oncology, 12 925-931 (2019)
Cancer can be considered the result of a series of genetic variations that lead to a normal cell being transformed into a malignant one while avoiding cell death¿atypical characte... [more]
Cancer can be considered the result of a series of genetic variations that lead to a normal cell being transformed into a malignant one while avoiding cell death¿atypical characteristics of tumor development. Although a large number of genomics and epigenetic alterations have been identified in cells undergoing apoptotic, autophagic or necrotic cell death, the treatment of cancer remains thought-provoking. Pyroptosis is differentiated from other types of programmed cell death and is mainly activated by Caspase-1. To initiate pyroptosis, cells receive specific ¿death¿ messages, produce cytokines, swell, burst, and ultimately die. The deficiency of Caspase-1 expression may lead to inflammation-mediated tumor progression. Hence, the molecular mechanisms for the Caspase-1 activation in tumor tissues are yet to be exploited extensively. This review aims to summarise the latest discoveries about pyroptosis and its new exciting role in inducing cancer cell death.
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2019 |
Li Q, Wang Y, Wu S, Zhou Z, Ding X, Shi R, et al., 'CircACC1 Regulates Assembly and Activation of AMPK Complex under Metabolic Stress', CELL METABOLISM, 30 157-+ (2019) [C1]
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2019 |
Gao W, Zhang Y, Niu M, Bo Y, Li H, Xue X, et al., 'Identification of miR-145-5p-Centered Competing Endogenous RNA Network in Laryngeal Squamous Cell Carcinoma', PROTEOMICS, 19 (2019) [C1]
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2019 |
de Bock CE, Down M, Baidya K, Sweron B, Boyd AW, Fiers M, et al., 'T-cell acute lymphoblastic leukemia express a unique truncated FAT1 isoform that cooperates with NOTCH1 in leukemia development.', Haematologica, 104 e204-e207 (2019) [C1]
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2019 |
Khan MR, Bukhari I, Khan R, Hussain HMJ, Wu M, Thorne RF, et al., 'TP53LNC-DB, the database of lncRNAs in the p53 signalling network', Database, 2019 (2019)
The TP53 gene product, p53, is a pleiotropic transcription factor induced by stress, which functions to promote cell cycle arrest, apoptosis and senescence. Genome-wide profiling ... [more]
The TP53 gene product, p53, is a pleiotropic transcription factor induced by stress, which functions to promote cell cycle arrest, apoptosis and senescence. Genome-wide profiling has revealed an extensive system of long noncoding RNAs (lncRNAs) that is integral to the p53 signalling network. As a research tool, we implemented a public access database called TP53LNC-DB that annotates currently available information relating lncRNAs to p53 signalling in humans.
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2019 |
Yari H, Jin L, Teng L, Wang Y, Wu Y, Liu GZ, et al., 'LncRNA REG1CP promotes tumorigenesis through an enhancer complex to recruit FANCJ helicase for REG3A transcription', NATURE COMMUNICATIONS, 10 (2019) [C1]
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2019 |
Gao W, An C, Xue X, Zheng X, Niu M, Zhang Y, et al., 'Mass Spectrometric Analysis Identifies AIMP1 and LTA4H as FSCN1-Binding Proteins in Laryngeal Squamous Cell Carcinoma', PROTEOMICS, 19 (2019) [C1]
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2019 |
Hu W, Chen S, Thorne RF, Wu M, 'TP53, TP53 Target Genes (DRAM, TIGAR), and Autophagy 127-149 (2019)
The tumor suppressor gene Tp53 encodes p53, a pivotal transcription factor with a broad target gene repertoire. Induction and stabilization of p53 during DNA damage and oncogene a... [more]
The tumor suppressor gene Tp53 encodes p53, a pivotal transcription factor with a broad target gene repertoire. Induction and stabilization of p53 during DNA damage and oncogene activation function to induce cell cycle arrest, apoptosis, or senescence. These actions are a failsafe to counteract carcinogenesis but Tp53 also plays a key role in regulating different aspects of cell metabolism including autophagy. Autophagy or cellular ¿self-eating¿ involves the dismantling and remodeling of cellular components, activities which are fundamental in maintaining cellular homeostasis and in supporting cell growth. After providing an historical overview of Tp53 research, the purpose of this chapter is to review the different mechanistic aspects of Tp53¿s role in autophagy and to highlight the key challenges which lie ahead. Tp53 functions are regulated by tight control of its cellular levels and notably, Tp53 can be both an activator or inhibitor of autophagy. Under stress conditions such as nutrient depletion or hypoxia, Tp53 contributes to autophagic activation by inhibiting mTOR signaling. Alternatively, p53 can interact with death-associated protein kinase 1 (DAPK1), acting to stabilize nuclear p53 amongst other functions including activation of the key autophagic mediator, Beclin-1. Under normal physiological conditions, Tp53 can inhibit autophagosome formation but stress conditions can also result in Tp53-mediated promotion of autophagy, demonstrating that Tp53 actions are highly context dependent. Tp53 target genes also play key opposing roles in autophagy induction or inhibition such as DRAM and TIGAR, respectively. Finally, the role of Tp53 mutants in autophagy regulation are discussed.
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2019 |
Gao W, Zhang C, Li W, Li H, Sang J, Zhao Q, et al., 'Promoter Methylation-Regulated miR-145-5p Inhibits Laryngeal Squamous Cell Carcinoma Progression by Targeting FSCN1', MOLECULAR THERAPY, 27 365-379 (2019) [C1]
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2019 |
Ahmed AF, de Bock CE, Sontag E, Hondermarck H, Lincz LF, Thorne RF, 'FAT1 cadherin controls neuritogenesis during NTera2 cell differentiation', Biochemical and Biophysical Research Communications, 514 625-631 (2019) [C1]
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2018 |
Gao F, Griffin N, Faulkner S, Rowe CW, Williams L, Roselli S, et al., 'The neurotrophic tyrosine kinase receptor TrkA and its ligand NGF are increased in squamous cell carcinomas of the lung', SCIENTIFIC REPORTS, 8 (2018) [C1]
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2018 |
Alkhatatbeh MJ, Enjeti AK, Baqar S, Ekinci EI, Liu D, Thorne RF, Lincz LF, 'Strategies for enumeration of circulating microvesicles on a conventional flow cytometer: Counting beads and scatter parameters.', Journal of Circulating Biomarkers, 7 1-10 (2018) [C1]
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2018 |
Sang B, Zhang YY, Guo ST, Kong LF, Cheng Q, Liu GZ, et al., 'Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence', Proceedings of the National Academy of Sciences of the United States of America, 115 E11661-E11670 (2018) [C1]
Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in c... [more]
Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in cancer cells resistant to either TNF-related apoptosis-inducing ligand (TRAIL) or the Mcl-1 inhibitor UMI-77, agents that act through the extrinsic and intrinsic apoptotic pathways, respectively. This work identified a commonly up-regulated lncRNA, ovarian adenocarcinoma-amplified lncRNA (OVAAL), that conferred apoptotic resistance in multiple cancer types. Analysis of clinical samples revealed OVAAL expression was significantly increased in colorectal cancers and melanoma in comparison to the corresponding normal tissues. Functional investigations showed that OVAAL depletion significantly inhibited cancer cell proliferation and retarded tumor xenograft growth. Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1. The ternary complex OVAAL/STK3/Raf-1 enhanced the activation of the RAF protooncogene serine/threonine-protein kinase (RAF)/mito-gen-activated protein kinase kinase 1 (MEK)/ERK signaling cascade, thus promoting c-Myc¿mediated cell proliferation and Mcl-1¿mediated cell survival. On the other hand, depletion of OVAAL triggered cellular senescence through polypyrimidine tract-binding protein 1 (PTBP1)¿mediated p27 expression, which was regulated by competitive binding between OVAAL and p27 mRNA to PTBP1. Additionally, c-Myc was demonstrated to drive OVAAL transcription, indicating a positive feedback loop between c-Myc and OVAAL in controlling tumor growth. Taken together, these results reveal that OVAAL contributes to the survival of cancer cells through dual mechanisms controlling RAF/MEK/ERK signaling and p27-mediated cell senescence.
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2018 |
Hu WL, Jin L, Xu A, Wang YF, Thorne RF, Zhang XD, Wu M, 'GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability.', Nature Cell Biology, 20 492-502 (2018) [C1]
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2018 |
La T, Liu GZ, Farrelly M, Cole N, Feng YC, Zhang YY, et al., 'A p53-responsive miRNA network promotes cancer cell quiescence', Cancer Research, 78 6666-6679 (2018) [C1]
Cancer cells in quiescence (G phase) are resistant to death, and re-entry of quiescent cancer cells into the cell-cycle plays an important role in cancer recurrence. Here we show... [more]
Cancer cells in quiescence (G phase) are resistant to death, and re-entry of quiescent cancer cells into the cell-cycle plays an important role in cancer recurrence. Here we show that two p53-responsive miRNAs utilize distinct but complementary mechanisms to promote cancer cell quiescence by facilitating stabilization of p27. Purified quiescent B16 mouse melanoma cells expressed higher levels of miRNA-27b-3p and miRNA-455-3p relative to their proliferating counterparts. Induction of quiescence resulted in increased levels of these miRNAs in diverse types of human cancer cell lines. Inhibition of miRNA-27b-3p or miRNA-455-3p reduced, whereas its overexpression increased, the proportion of quiescent cells in the population, indicating that these miRNAs promote cancer cell quiescence. Accordingly, cancer xenografts bearing miRNA-27b-3p or miRNA-455-3p mimics were retarded in growth. miRNA-27b-3p targeted cyclin-dependent kinase regulatory subunit 1 (CKS1B), leading to reduction in p27 polyubiquitination mediated by S-phase kinase-associated protein 2 (Skp2). miRNA-455-3p targeted CDK2-associated cullin domain 1 (CAC1), which enhanced CDK2-mediated phosphorylation of p27 necessary for its polyubiquitination. Of note, the gene encoding miRNA-27b-3p was embedded in the intron of the chromosome 9 open reading frame 3 gene that was transcriptionally activated by p53. Similarly, the host gene of miRNA-455-3p, collagen alpha-1 (XXVII) chain, was also a p53 transcriptional target. Collectively, our results identify miRNA-27b-3p and miRNA-455-3p as important regulators of cancer cell quiescence in response to p53 and suggest that manipulating miRNA-27b-3p and miRNA-455-3p may constitute novel therapeutic avenues for improving outcomes of cancer treatment. Significance: Two novel p53-responsive microRNAs whose distinct mechanisms of action both stabilize p27 to promote cell quiescence and may serve as therapeutic avenues for improving outcomes of cancer treatment. 0
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2018 |
Faulkner S, Jobling P, Rowe CW, Rodrigues Oliveira SM, Roselli S, Thorne RF, et al., 'Neurotrophin Receptors TrkA, p75
Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor k... [more]
Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor kinase TrkA (also called NTRK1), the common neurotrophin receptor p75 , and the proneurotrophin receptor sortilin were analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples (P = 0.0007). TrkA expression was independent of histologic subtypes but associated with lymph node metastasis (P = 0.0148), suggesting the involvement of TrkA in tumor invasiveness. Nerves in the tumor microenvironment were positive for TrkA. p75 was overexpressed in anaplastic thyroid cancers compared with papillary and follicular subtypes (P < 0.0001). Sortilin was overexpressed in thyroid cancers compared with benign thyroid tissues (P < 0.0001). Neurotrophin receptor expression was confirmed in a panel of thyroid cancer cell lines at the mRNA and protein levels. Functional investigations using the anaplastic thyroid cancer cell line CAL-62 found that siRNA against TrkA, p75 , and sortilin decreased cell survival and cell migration through decreased SRC and ERK activation. Together, these data reveal TrkA, p75 , and sortilin as potential therapeutic targets in thyroid cancer. NTR NTR NTR NTR
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2018 |
Xiang S, Gu H, Jin L, Thorne RF, Zhang XD, Wu M, 'LncRNA IDH1-AS1 links the functions of c-Myc and HIF1a via IDH1 to regulate the Warburg effect', Proceedings of the National Academy of Sciences of the United States of America, 115 E1465-E1474 (2018) [C1]
The oncoprotein c-Myc plays an important role in regulating glycolysis under normoxia; yet, in cancer cells, HIF1a, which is essential for driving glycolysis under hypoxia, is oft... [more]
The oncoprotein c-Myc plays an important role in regulating glycolysis under normoxia; yet, in cancer cells, HIF1a, which is essential for driving glycolysis under hypoxia, is often up-regulated even in the presence of oxygen. The relationship between these two major regulators of the Warburg effect remains to be fully defined. Here we demonstrate that regulation of a long noncoding RNA (lncRNA), named IDH1-AS1, enables c-Myc to collaborate with HIF1a in activating the Warburg effect under normoxia. c-Myc transcriptionally repressed IDH1-AS1, which, upon expression, promoted homodimerization of IDH1 and thus enhanced its enzymatic activity. This resulted in increased a-KG and decreased ROS production and subsequent HIF1a down-regulation, leading to attenuation of glycolysis. Hence, c-Myc repression of IDH1-AS1 promotes activation of the Warburg effect by HIF1a. As such, IDH1-AS1 overexpression inhibited cell proliferation, whereas silencing of IDH1-AS1 promoted cell proliferation and cancer xenograft growth. Restoring IDH1-AS1 expression may therefore represent a potential metabolic approach for cancer treatment.
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2018 |
Martin D, Degese MS, Vitale-Cross L, Iglesias-Bartolome R, Valera JLC, Wang Z, et al., 'Assembly and activation of the Hippo signalome by FAT1 tumor suppressor', NATURE COMMUNICATIONS, 9 (2018) [C1]
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2018 |
Zhang YY, Tabataba H, Liu XY, Wang JY, Yan XG, Farrelly M, et al., 'ACTN4 regulates the stability of RIPK1 in melanoma', ONCOGENE, 37 4033-4045 (2018) [C1]
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2017 |
Guo ST, Guo XY, Wang J, Wang CY, Yang RH, Wang FH, et al., 'MicroRNA-645 is an oncogenic regulator in colon cancer', ONCOGENESIS, 6 (2017) [C1]
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2017 |
Wang JY, Liu GZ, Wilmott JS, La T, Feng YC, Yari H, et al., 'Skp2-mediated stabilization of MTH1 promotes survival of melanoma cells upon oxidative stress', Cancer Research, 77 6226-6239 (2017) [C1]
MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA; however, there is little understanding of how MTH1 itself is regulated. Here, we report that MTH1 is reg... [more]
MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA; however, there is little understanding of how MTH1 itself is regulated. Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination. In melanoma cell lines and patient specimens, we observed a positive correlation of Skp2 and MTH1 expression. Mechanistic investigations showed that Skp2 limited DNA damage and apoptosis triggered by oxidative stress and that MAPK upregulated Skp2 and MTH1 to render cells more resistant to such stress. Collectively, our findings identify Skp2-mediated K63-linked polyubiquitination as a critical regulatory mechanism responsible for MTH1 upregulation in melanoma, with potential implications to target the MAPK/Skp2/MTH1 pathway to improve its treatment.
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2017 |
Liu F, Jiang CC, Yan XG, Tseng H-Y, Wang CY, Zhang YY, et al., 'BRAF/MEK inhibitors promote CD47 expression that is reversible by ERK inhibition in melanoma.', Oncotarget, 8 69477-69492 (2017) [C1]
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2017 |
Liu F, Jiang CC, Yan XG, Tseng H-Y, Wang CY, Zhang YY, et al., 'BRAF/MEK inhibitors promote CD47 expression that is reversible by ERK inhibition in melanoma.', Oncotarget, 8 69477-69492 (2017) [C1]
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2017 |
Alkhatatbeh MJ, Lincz LF, Thorne RF, 'Bio-maleimide-stained plasma microparticles can be purified in a native state and target human proximal tubular HK2 cells', BIOMEDICAL REPORTS, 6 63-68 (2017) [C1]
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2017 |
de Bock CE, Hughes MR, Snyder K, Alley S, Sadeqzadeh E, Dun MD, et al., 'Protein interaction screening identifies SH3RF1 as a new regulator of FAT1 protein levels', FEBS LETTERS, 591 667-678 (2017) [C1]
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2016 |
Alkhatatbeh MJ, Lincz LF, Thorne RF, 'Low simvastatin concentrations reduce oleic acid-induced steatosis in HepG
Non-alcoholic fatty liver disease (NAFLD) is an inflammatory condition caused by hepatic lipid accumulation that is associated with insulin resistance, diabetes and metabolic synd... [more]
Non-alcoholic fatty liver disease (NAFLD) is an inflammatory condition caused by hepatic lipid accumulation that is associated with insulin resistance, diabetes and metabolic syndrome. Although statins should be used with caution in liver diseases, they are increasingly investigated as a possible treatment for NAFLD. The present study recreated an in vitro model of NAFLD using HepG cells exposed to oleic acid (OA), which was used to quantify OA-induced lipid accumulation in HepG cells treated with various concentrations of simvastatin. In addition, the effect of simvastatin on HepG cell morphology and microparticle generation as a marker of cell apoptosis was assessed. OA-induced lipid accumulation was quantified by Oil Red O staining and extraction for optical density determination. Stained lipid droplets were visualized using phase contrast microscopy. Furthermore, HepG cell-derived microparticles were counted by flow cytometry subsequent to staining for Annexin V. HepG cells treated with 0-1 mM OA showed dose-dependent lipid accumulation. Treatment of HepG cells with increasing concentrations of simvastatin followed by treatment with 1 mM OA showed that low simvastatin concen- trations (4-10 µM) were able to reduce lipid accumulation by ~40%, whereas high simvastatin concentrations (20 and 30 µM) induced apoptotic changes in cell morphology and increased the production of Annexin V microparticles. This suggests that low simvastatin doses may have a role in preventing NAFLD. However, further investigations are required to confirm this action in vivo and to determine the underlying mechanism by which simvastatin reduces hepatic steatosis. 2 2 2 2 2 2 +
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2016 |
Phang M, Thorne RF, Alkhatatbeh MJ, Garg ML, Lincz LF, 'Circulating CD36+microparticles are not altered by docosahexaenoic or eicosapentaenoic acid supplementation', NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES, 26 254-260 (2016) [C1]
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2016 |
de Bock CE, Thorne RE, 'CELL BIOLOGY A mitochondrial brake on vascular repair', NATURE, 539 503-505 (2016)
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2016 |
Guo ST, Chi MN, Yang RH, Guo XY, Zan LK, Wang CY, et al., 'INPP4B is an oncogenic regulator in human colon cancer', Oncogene, 35 3049-3061 (2016) [C1]
Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we ... [more]
Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum-and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease.
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2015 |
Zouikr I, Ahmed AF, Horvat JC, Beagley KW, Clifton VL, Ray A, et al., 'Programming of formalin-induced nociception by neonatal LPS exposure: Maintenance by peripheral and central neuroimmune activity', Brain, Behavior, and Immunity, 44 235-246 (2015) [C1]
The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of develop... [more]
The immune and nociceptive systems are shaped during the neonatal period where they undergo fine-tuning and maturation. Painful experiences during this sensitive period of development are known to produce long-lasting effects on the immune and nociceptive responses. It is less clear, however, whether inflammatory pain responses are primed by neonatal exposure to mild immunological stimuli, such as with lipopolysaccharide (LPS). Here, we examine the impact of neonatal LPS exposure on inflammatory pain responses, peripheral and hippocampal interleukin-1ß (IL-1ß), as well as mast cell number and degranulation in preadolescent and adult rats. Wistar rats were injected with LPS (0.05 mg/kg IP, Salmonella enteritidis) or saline on postnatal days (PNDs) 3 and 5 and later subjected to the formalin test at PNDs 22 and 80-97. At both time-points, and one-hour after formalin injection, blood and hippocampus were collected for measuring circulating and central IL-1ß levels using ELISA and Western blot, respectively. Paw tissue was also isolated to assess mast cell number and degree of degranulation using Toluidine Blue staining. Behavioural analyses indicate that at PND 22, LPS-challenged rats displayed enhanced flinching (p<.01) and licking (p<.01) in response to formalin injection. At PNDs 80-97, LPS-challenged rats exhibited increased flinching (p<.05), an effect observed in males only. Furthermore, neonatal LPS exposure enhanced circulating IL-1ß and mast cell degranulation in preadolescent but not adult rats following formalin injection. Hippocampal IL-1ß levels were increased in LPS-treated adult but not preadolescent rats in response to formalin injection. These data suggest neonatal LPS exposure produces developmentally regulated changes in formalin-induced behavioural responses, peripheral and central IL-1ß levels, as well as mast cell degranulation following noxious stimulation later in life. These findings highlight the importance of immune activation during the neonatal period in shaping immune response and pain sensitivity later in life. This is of clinical relevance given the high prevalence of bacterial infection during the neonatal period, particularly in the vulnerable population of preterm infants admitted to neonatal intensive care units.
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2015 |
Pundavela J, Roselli S, Faulkner S, Attia J, Scott RJ, Thorne RF, et al., 'Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer', Molecular Oncology, 9 1626-1635 (2015) [C1]
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2015 |
Ahmed AF, De Bock CE, Lincz LF, Pundavela J, Zouikr I, Sontag E, et al., 'FAT1 cadherin acts upstream of Hippo signalling through TAZ to regulate neuronal differentiation', Cellular and Molecular Life Sciences, 72 4653-4669 (2015) [C1]
The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are ... [more]
The Hippo pathway is emerging as a critical nexus that balances self-renewal of progenitors against differentiation; however, upstream elements in vertebrate Hippo signalling are poorly understood. High expression of Fat1 cadherin within the developing neuroepithelium and the manifestation of severe neurological phenotypes in Fat1-knockout mice suggest roles in neurogenesis. Using the SH-SY5Y model of neuronal differentiation and employing gene silencing techniques, we show that FAT1 acts to control neurite outgrowth, also driving cells towards terminal differentiation via inhibitory effects on proliferation. FAT1 actions were shown to be mediated through Hippo signalling where it activated core Hippo kinase components and antagonised functions of the Hippo effector TAZ. Suppression of FAT1 promoted the nucleocytoplasmic shuttling of TAZ leading to enhanced transcription of the Hippo target gene CTGF together with accompanying increases in nuclear levels of Smad3. Silencing of TAZ reversed the effects of FAT1 depletion thus connecting inactivation of TAZ-TGFbeta signalling with Hippo signalling mediated through FAT1. These findings establish FAT1 as a new upstream Hippo element regulating early stages of differentiation in neuronal cells.
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2014 |
Pundavela J, Demont Y, Jobling P, Lincz LF, Roselli S, Thorne RF, et al., 'ProNGF correlates with Gleason score and is a potential driver of nerve infiltration in prostate cancer', American Journal of Pathology, 184 3156-3162 (2014) [C1]
Nerve infiltration is essential to prostate cancer progression, but the mechanism by which nerves are attracted to prostate tumors remains unknown. We report that the precursor of... [more]
Nerve infiltration is essential to prostate cancer progression, but the mechanism by which nerves are attracted to prostate tumors remains unknown. We report that the precursor of nerve growth factor (proNGF) is overexpressed in prostate cancer and involved in the ability of prostate cancer cells to induce axonogenesis. A series of 120 prostate cancer and benign prostate hyperplasia (BPH) samples were analyzed by IHC for proNGF. ProNGF was mainly localized in the cytoplasm of epithelial cells, with marked expression in cancer compared with BPH. Importantly, the proNGF level positively correlated with the Gleason score (n = 104, t<inf>B</inf> = 0.51). A higher level of proNGF was observed in tumors with a Gleason score of =8 compared with a Gleason score of 7 and 6 (P < 0.001). In vitro, proNGF was detected in LNCaP, DU145, and PC-3 prostate cancer cells and BPH-1 cells but not in RWPE-1 immortalized nontumorigenic prostate epithelial cells or primary normal prostate epithelial cells. Co-culture of PC12 neuronal-like cells or 50B11 neurons with PC-3 cells resulted in neurite outgrowth in neuronal cells that was inhibited by blocking antibodies against proNGF, indicating that prostate cancer cells can induce axonogenesis via secretion of proNGF. These data reveal that ProNGF is a biomarker associated with high-risk prostate cancers and a potential driver of infiltration by nerves.
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2014 |
Sadeqzadeh E, De Bock CE, Wojtalewicz N, Holt JE, Smith ND, Dun MD, et al., 'Furin processing dictates ectodomain shedding of human FAT1 cadherin', Experimental Cell Research, 323 41-55 (2014) [C1]
Fat1 is a single pass transmembrane protein and the largest member of the cadherin superfamily. Mouse knockout models and in vitro studies have suggested that Fat1 influences cell... [more]
Fat1 is a single pass transmembrane protein and the largest member of the cadherin superfamily. Mouse knockout models and in vitro studies have suggested that Fat1 influences cell polarity and motility. Fat1 is also an upstream regulator of the Hippo pathway, at least in lower vertebrates, and hence may play a role in growth control. In previous work we have established that FAT1 cadherin is initially cleaved by proprotein convertases to form a noncovalently linked heterodimer prior to expression on the cell surface. Such processing was not a requirement for cell surface expression, since melanoma cells expressed both unprocessed FAT1 and the heterodimer on the cell surface. Here we further establish that the site 1 (S1) cleavage step to promote FAT1 heterodimerisation is catalysed by furin and we identify the cleavage site utilised. For a number of other transmembrane receptors that undergo heterodimerisation the S1 processing step is thought to occur constitutively but the functional significance of heterodimerisation has been controversial. It has also been generally unclear as to the significance of receptor heterodimerisation with respect to subsequent post-translational proteolysis that often occurs in transmembrane proteins. Exploiting the partial deficiency of FAT1 processing in melanoma cells together with furin-deficient LoVo cells, we manipulated furin expression to demonstrate that only the heterodimer form of FAT1 is subject to cleavage and subsequent release of the extracellular domain. This work establishes S1-processing as a clear functional prerequisite for ectodomain shedding of FAT1 with general implications for the shedding of other transmembrane receptors. © 2014.
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2014 |
Sadeqzadeh E, de Bock CE, O'Donnell MR, Timofeeva A, Burns GF, Thorne RF, 'FAT1 cadherin is multiply phosphorylated on its ectodomain but phosphorylation is not catalysed by the four-jointed homologue', FEBS LETTERS, 588 3511-3517 (2014) [C1]
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2014 |
Sadeqzadeh E, De Bock CE, Thorne RF, 'Sleeping Giants: Emerging Roles for the Fat Cadherins in Health and Disease', Medicinal Research Reviews, 34 190-221 (2014) [C1]
The vertebrate Fat cadherins comprise a small gene family of four members, Fat1-Fat4, all closely related in structure to Drosophila ft and ft2. Over the past decade, knock-out mo... [more]
The vertebrate Fat cadherins comprise a small gene family of four members, Fat1-Fat4, all closely related in structure to Drosophila ft and ft2. Over the past decade, knock-out mouse studies, genetic manipulation, and large sequencing projects has aided our understanding of the function of vertebrate Fat cadherins in tissue development and disease. The majority of studies of this family have focused on Fat1, with evidence now showing it can bind enable (ENA)/Vasodilator-stimulated phosphoprotein (VASP), ß-catenin and Atrophin proteins to influence cell polarity and motility; HOMER-1 and HOMER-3 proteins to regulate actin accumulation in neuronal synapses; and scribble to influence the Hippo signaling pathway. Fat2 and Fat3 can regulate cell migration in a tissue specific manner and Fat4 appears to influence both planar cell polarity and Hippo signaling recapitulating the activity of Drosophila ft. Knowledge about the exact downstream signaling pathways activated by each family member remains in its infancy, but it is becoming clearer that they have tissue specific and redundant roles in development and may be lost or gained in cancer. In this review, we summarize the recent progress on understanding the role of the Fat cadherin family, integrating the current knowledge of molecular interactions and tissue distributions, together with the accumulating evidence of their changed expression in human disease. The latter is now beginning to promote interest in these molecules as both biomarkers and new targets for therapeutic intervention. © 2013 Wiley Periodicals, Inc.
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2014 |
Mhaidat NM, Bouklihacene M, Thorne RF, '5-Fluorouracil-induced apoptosis in colorectal cancer cells is caspase-9-dependent and mediated by activation of protein kinase C-d', Oncology Letters, 8 699-704 (2014) [C1]
Elucidation of the molecular mechanisms by which 5-fluorouracil (5-FU) induces apoptosis is required in order to understand the resistance of colorectal cancer (CRC) cells to 5-FU... [more]
Elucidation of the molecular mechanisms by which 5-fluorouracil (5-FU) induces apoptosis is required in order to understand the resistance of colorectal cancer (CRC) cells to 5-FU. In the current study, 5-FU-induced apoptosis was assessed using the propidium iodide method. Involvement of protein kinase C (PKC) was assessed by evaluating the extent of their activation in CRC, following treatment with 5-FU, using biochemical inhibitors and western blot analysis. The results revealed that 5-FU induces varying degrees of apoptosis in CRC cells; HCT116 cells were identified to be the most sensitive cells and SW480 were the least sensitive. In addition, 5-FU-induced apoptosis was caspase-dependent as it appeared to be initiated by caspase-9. Furthermore, PKCe was marginally expressed in CRC cells and no changes were observed in the levels of cleavage or phosphorylation following treatment with 5-FU. The treatment of HCT116 cells with 5-FU increased the expression, phosphorylation and cleavage of PKCd. The inhibition of PKCd was found to significantly inhibit 5-FU-induced apoptosis. These results indicated that 5-FU induces apoptosis in CRC by the activation of PKCd and caspase-9. In addition, the levels of PKCd activation may determine the sensitivity of CRC to 5-FU.
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2014 |
Vuong QV, Sadeqzadeh E, Hirun S, Goldsmith CD, Zammitt N, Bowyer MB, et al., 'Phenolic Compounds, Antioxidant and Anti-Cancer Properties of the Australian Maroon Bush Scaevola spinescens (Goodeniaceae)', Journal of Bioanalysis & Biomedicine, S12 (2014) [C1]
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2014 |
Wojtalewicz N, Sadeqzadeh E, Weiss JV, Tehrani MM, Klein-Scory S, Hahn S, et al., 'A Soluble Form of the Giant Cadherin Fat1 Is Released from Pancreatic Cancer Cells by ADAM10 Mediated Ectodomain Shedding', PLOS ONE, 9 (2014) [C1]
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2014 |
Oliveira CS, de Bock CE, Molloy TJ, Sadeqzadeh E, Geng XY, Hersey P, et al., 'Macrophage migration inhibitory factor engages PI3K/Akt signalling and is a prognostic factor in metastatic melanoma', BMC Cancer, 14 (2014) [C1]
Background: Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in a variety of cellular processes including cell cycle regulation and the control... [more]
Background: Macrophage migration inhibitory factor (MIF) is a widely expressed cytokine involved in a variety of cellular processes including cell cycle regulation and the control of proliferation. Overexpression of MIF has been reported in a number of cancer types and it has previously been shown that MIF is upregulated in melanocytic tumours with the highest expression levels occurring in malignant melanoma. However, the clinical significance of high MIF expression in melanoma has not been reported. Methods: MIF expression was depleted in human melanoma cell lines using siRNA-mediated gene knockdown and effects monitored using in vitro assays of proliferation, cell cycle, apoptosis, clonogenicity and Akt signalling. In silico analyses of expression microarray data were used to correlate MIF expression levels in melanoma tumours with overall patient survival using a univariate Cox regression model. Results: Knockdown of MIF significantly decreased proliferation, increased apoptosis and decreased anchorage-independent growth. Effects were associated with reduced numbers of cells entering S phase concomitant with decreased cyclin D1 and CDK4 expression, increased p27 expression and decreased Akt phosphorylation. Analysis of clinical outcome data showed that MIF expression levels in primary melanoma were not associated with outcome (HR = 1.091, p = 0.892) whereas higher levels of MIF in metastatic lesions were significantly associated with faster disease progression (HR = 2.946, p = 0.003 and HR = 4.600, p = 0.004, respectively in two independent studies). Conclusions: Our in vitro analyses show that MIF functions upstream of the PI3K/Akt pathway in human melanoma cell lines. Moreover, depletion of MIF inhibited melanoma proliferation, viability and clonogenic capacity. Clinically, high MIF levels in metastatic melanoma were found to be associated with faster disease recurrence. These findings support the clinical significance of MIF signalling in melanoma and provide a strong rationale for both targeting and monitoring MIF expression in clinical melanoma.
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2013 |
Li J, Imtiaz MS, Beard NA, Dulhunty AF, Thorne R, vanHelden DF, Laver DR, 'ß-Adrenergic stimulation increases RyR2 activity via intracellular Ca2+ and Mg2+ regulation.', PLoS One, 8 e58334 (2013) [C1]
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2013 |
Mhaidat NM, Qandil AM, Al-Balas QA, Hassan MA, Jaradat SA, Matalkah AM, Thorne RT, 'Methoxyphenylcipro induces antitumor activity in human cancer cells', Archives of Pharmacal Research, 36 1023-1028 (2013) [C1]
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2013 |
Guo ST, Jiang CC, Wang GP, Li YP, Wang CY, Guo XY, et al., 'MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer', ONCOGENE, 32 1910-1920 (2013) [C1]
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2013 |
Ardjmand A, de Bock CE, Shahrokhi S, Lincz LF, Boyd AW, Burns GF, Thorne RF, 'Fat1 cadherin provides a novel minimal residual disease marker in acute lymphoblastic leukemia', HEMATOLOGY, 18 315-321 (2013) [C1]
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2013 |
Ye Y, Jin L, Wilmott JS, Hu WL, Yosufi B, Thorne RF, et al., 'PI(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma', NATURE COMMUNICATIONS, 4 (2013) [C1]
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2013 |
Alkhatatbeh MJ, Enjeti AK, Acharya S, Thorne RF, Lincz LF, 'The origin of circulating CD36 in type 2 diabetes', NUTRITION & DIABETES, 3 (2013) [C1]
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2012 |
De Bock CE, Ardjmand Ghahestani A, Molloy TJ, Bone SM, Johnstone DM, Campbell DM, et al., 'The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis-relapse samples of precursor B-cell acute lymphoblastic leukemia', Leukemia, 26 918-926 (2012) [C1]
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2012 |
Mhaidat NM, Abdul-Razzak KK, Alkofahi AS, Alsarhan AM, Aldaher AN, Thorne RF, 'Altholactone induces apoptotic cell death in human colorectal cancer cells', Phytotherapy Research, 26 926-931 (2012) [C1]
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2012 |
Tay KH, Jin L, Tseng HY, Jiang CC, Ye Y, Thorne RF, et al., 'Suppression of PP2A is critical for protection of melanoma cells upon endoplasmic reticulum stress', Cell Death and Disease, 3 (2012) [C1]
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2011 |
Alkhatatbeh MJ, Mhaidat NM, Enjeti AK, Lincz L, Thorne RF, 'The putative diabetic plasma marker, soluble CD36, is non-cleaved, non-soluble and entirely associated with microparticles', Journal of Thrombosis and Haemostasis, 9 844-851 (2011) [C1]
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2011 |
Jiang CC, Lai F, Thorne RF, Yang F, Liu H, Hersey P, Zhang XD, 'MEK-independent survival of B-RAFV600E melanoma cells selected for resistance to apoptosis induced by the RAF inhibitor PLX4720', Clinical Cancer Research, 17 721-730 (2011) [C1]
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2011 |
Sadeqzadeh E, De Bock CE, Zhang XD, Shipman KL, Scott NM, Song C, et al., 'Dual processing of FAT1 cadherin protein by human melanoma cells generates distinct protein products', Journal of Biological Chemistry, 286 28181-28191 (2011) [C1]
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2011 |
Jin L, Hu WL, Jiang CC, Wang JX, Han CC, Chu P, et al., 'MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma', Proceedings of the National Academy of Sciences, 108 15840-15845 (2011) [C1]
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2011 |
Dong L, Jiang CC, Thorne RF, Croft A, Yang F, Liu H, et al., 'Ets-1 mediates upregulation of Mcl-1 downstream of XBP-1 in human melanoma cells upon ER stress', Oncogene, 30 3716-3726 (2011) [C1]
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2010 |
Tseng H-Y, Jiang CC, Croft A, Croft A, Thorne RF, Yang F, et al., 'Contrasting effects of Nutlin-3 on TRAIL - and Docetaxel-induced Apoptosis due to upregulation of TRAIL-R2 and Mcl-1 in human melanoma cells', Molecular Cancer Therapeutics, 9 3363-3374 (2010) [C1]
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2010 |
Zhang X, Thorne RF, Wagner TE, Wei Y, 'Regulatory T cells and cancer therapy: An old story with a new hope', Current Cancer Therapy Reviews, 6 34-40 (2010) [C1]
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2010 |
Jiang CC, Lai F, Tay KH, Croft A, Rizos H, Becker TM, et al., 'Apoptosis of human melanoma cells induced by inhibition of B-RAF(V600E) involves preferential splicing of bim(S)', Cell Death & Disease, 1 e69 (2010) [C1]
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2010 |
Thorne RF, Ralston KJ, De Bock CE, Mhaidat NM, Zhang XD, Boyd AW, Burns GF, 'Palmitoylation of CD36/FAT regulates the rate of its post-transcriptional processing in the endoplasmic reticulum', Biochimica et Biophysica Acta - Molecular Cell Research, 1803 1298-1307 (2010) [C1]
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2010 |
Yang F, Tay KH, Dong L, Thorne RF, Jiang CC, Yang E, et al., 'Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIPL from degradation by the E3 ligase itch in human melanoma cells', Cell Death and Differentiation, 17 1354-1367 (2010) [C1]
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2010 |
Mao ZG, Jiang CC, Thorne RF, Hersey P, Zhang XD, 'TRAIL-induced apoptosis of human melanoma cells involves activation of caspase-4', Apoptosis, 15 1211-1222 (2010) [C1]
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2009 |
Jiang CC, Yang F, Thorne RF, Zhu BK, Hersey P, Zhang XD, 'Human melanoma cells under endoplasmic reticulum stress acquire resistance to microtubule-targeting drugs through XBP-1-mediated activation of Akt', Neoplasia, 11 436-447 (2009) [C1]
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2009 |
Zhang LJ, Chen S, Wu P, Hu CS, Thorne RF, Luo CM, et al., 'Inhibition of MEK blocks GRP78 up-regulation and enhances apoptosis induced by ER stress in gastric cancer cells', Cancer Letters, 274 40-46 (2009) [C1]
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2009 |
Mhaidat NM, Alali FQ, Matalqah SM, Matalka II, Jaradat SA, Al-Sawalha NA, Thorne RF, 'Inhibition of MEK sensitizes paclitaxel-induced apoptosis of human colorectal cancer cells by downregulation of GRP78', Anti-Cancer Drugs, 20 601-606 (2009) [C1]
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2008 |
Mhaidat NM, Thorne RF, Zhang XD, Hersey P, 'Involvement of endoplasmic reticulum stress in Docetaxel-induced JNK-dependent apoptosis of human melanoma', Apoptosis, 13 1505-1512 (2008) [C1]
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2008 |
Chen LH, Jiang CC, Watts R, Thorne RF, Kiejda KA, Zhang XD, Hersey P, 'Inhibition of endoplasmic reticulum stress-induced apoptosis of melanoma cells by the ARC protein', Cancer Research, 68 834-842 (2008) [C1]
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2008 |
Jiang CC, Lucas K, Kiejda KA, Wade M, Debock CE, Thorne RF, et al., 'Up-regulation of Mcl-1 is critical for survival of human melanoma cells upon endoplasmic reticulum stress', Cancer Research, 68 6708-6717 (2008) [C1]
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2008 |
Mhaidat NM, Thorne RF, De Bock CE, Zhang XD, Hersey P, 'Melanoma cell sensitivity to docetaxal-induced apoptosis is determined by class III beta-tubulin levels', FEBS Letters, 582 267-272 (2008) [C1]
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2008 |
Zhang LJ, Hao YZ, Hu CS, Ye Y, Xie QP, Thorne RF, et al., 'Inhibition of apoptosis facilitates necrosis induced by cisplatin in gastric cancer cells', Anti-Cancer Drugs, 19 159-166 (2008) [C1]
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2007 |
Mhaidat NM, Thorne RF, Zhang XD, Hersey P, 'Regulation of docetaxel-induced apoptosis of human melanoma cells by different isoforms of protein kinase C', Molecular Cancer Research, 5 1073-1081 (2007) [C1]
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2007 |
Thorne RF, Mhaidat N, Ralston KJ, Burns GF, 'Shed gangliosides provide detergent-independent evidence for type-3 glycosynapses', Biochemical and Biophysical Research Communications, 356 306-311 (2007) [C1]
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2007 |
Jiang CC, Li HC, Gillespie S, Kiejda KA, Mhaidat N, Yu FW, et al., 'Tunicamycin sensitizes human melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by up-regulation of TRAIL-R2 via the unfolded protein response', Cancer Research, 67 5880-5888 (2007) [C1]
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2007 |
Thorne RF, Mhaidat N, Ralston KJ, Burns GF, 'CD36 is a receptor for oxidized high density lipoprotein: Implications for the development of atherosclerosis', FEBS Letters, 581 1227-1232 (2007) [C1]
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2007 |
Chen LH, Jiang CC, Kiejda KA, Wang YF, Thorne RF, Zhang XD, Hersey P, 'Thapsigargin sensitizes human melanoma cells to TRAIL-induced apoptosis by up-regulation of TRAIL-R2 through the unfolded protein response', Carcinogenesis, 28 2328-2336 (2007) [C1]
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2006 |
Tzircotis G, Thorne RF, Isacke CM, 'Directional sensing of a phorbol ester gradient requires CD44 and is regulated by CD44 phosphorylation', Oncogene, 25 7401-7410 (2006) [C1]
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2006 |
Thorne RF, Zhang XH, Song CJ, Jin BQ, Burns GF, 'Novel immunoblotting monoclonal antibodies against human and rat CD36/fat used to identify an isoform of CD36 in rat muscle', DNA and Cell Biology, 25 302-311 (2006) [C1]
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2006 |
Thorne RF, Law E, Elith CA, Ralston KJ, Bates RC, Burns GF, 'The association between CD36 and Lyn protein tyrosine kinase is mediated by lipid', Biochemical and Biophysical Research Communications, 351 51-56 (2006) [C1]
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2005 |
Tzircotis G, Thorne RF, Isacke CM, 'Chemotaxis towards hyaluronan is dependent on CD44 expression and modulated by cell type variation in CD44-hyaluronan binding', Journal of Cell Science, 118 5119-5128 (2005) [C1]
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2004 |
Ralston KJ, Hird S, Zhang X, Scott JL, Jin B, Thorne RF, et al., 'The LFA-1-associated molecule PTA-1 (CD226) on T cells forms a dynamic molecular complex with protein 4.1G and human discs large', Journal of Biological Chemistry, 279 33816-33828 (2004) [C1]
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2004 |
Thorne RF, Legg JW, Isacke CM, 'The role of the CD44 transmembrane and cytoplasmic domains in co-ordinating adhesive and signalling events', JOURNAL OF CELL SCIENCE, 117 373-380 (2004) [C1]
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2004 |
Tzircotis G, Thorne RF, Isacke CM, 'A new spreadsheet method for the analysis of bivariate flow cytometric data', BMC Cell Biology, 5 (2004)
Background: A useful application of flow cytometry is the investigation of cell receptor-ligand interactions. However such analyses are often compromised due to problems interpret... [more]
Background: A useful application of flow cytometry is the investigation of cell receptor-ligand interactions. However such analyses are often compromised due to problems interpreting changes in ligand binding where the receptor expression is not constant. Commonly, problems are encountered due to cell treatments resulting in altered receptor expression levels, or when cell lines expressing a transfected receptor with variable expression are being compared. To overcome this limitation we have developed a Microsoft Excel spreadsheet that aims to automatically and effectively simplify flow cytometric data and perform statistical tests in order to provide a clearer graphical representation of results. Results: To demonstrate the use and advantages of this new spreadsheet method we have investigated the binding of the transmembrane adhesion receptor CD44 to its ligand hyaluronan. In the first example, phorbol ester treatment of cells results in both increased CD44 expression and increased hyaluronan binding. By applying the spreadsheet method we effectively demonstrate that this increased ligand binding results from receptor activation. In the second example we have compared AKR1 cells transfected either with wild type CD44 (WT CD44) or a mutant with a truncated cytoplasmic domain (CD44-T). These two populations do not have equivalent receptor expression levels but by using the spreadsheet method hyaluronan binding could be compared without the need to generate single cell clones or FACS sorting the cells for matching CD44 expression. By this method it was demonstrated that hyaluronan binding requires a threshold expression of CD44 and that this threshold is higher for CD44-T. However, at high CD44-T expression, binding was equivalent to WT CD44 indicating that the cytoplasmic domain has a role in presenting the receptor at the cell surface in a form required for efficient hyaluronan binding rather than modulating receptor activity. Conclusion: Using the attached spreadsheets and instructions, a simple post-acquisition method for analysing bivariate flow cytometry data is provided. This method constitutes a straightforward improvement over the standard graphical output of flow cytometric data and has the significant advantage that ligand binding can be compared between cell populations irrespective of receptor expression levels. © 2004 Tzircotis et al; licensee BioMed Central Ltd.
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2003 |
Sullivan A, Uff CR, Isacke CM, Thorne RF, 'PACE-1, a novel protein that interacts with the C-terminal domain of ezrin', EXPERIMENTAL CELL RESEARCH, 284 224-238 (2003) [C1]
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2000 |
Gruarin P, Thorne R, Dorahy DJ, Burns G, Sitia R, Alessio M, 'CD36 is a Ditopic Glycoprotein with the N-Terminal Domain Implicated in Intracellular Transport', Biochemical and Biophysical Research Communications, 275 446-454 (2000) [C1]
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2000 |
Thorne R, Marshall J, Shafren D, Gibson PG, Hart I, Burns G, 'The Integrins a3B1 and a6B1 Physically and Functionally Associate with CD36 in Human Melanoma Cells', Journal of Biological Chemistry, 275 35264-35275 (2000) [C1]
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2000 |
Thorne RF, Marshall J, Shafren D, Gibson P, Hart I, Burns GF, 'The Integrins (alpha)3(beta)1 Physically and functionally Associate with CD36 in Human Melanoma Cells', The Journal of Biological Chemistry, 275 No. 45 35264-35275 (2000) [C1] |
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2000 |
Shafren D, Dorahy DJ, Thorne R, Barry R, 'Cytoplasmic interactions between decay-accelerating factor and intercellular adhesion molecule-1 are not required for coxsackievirus A21 cell infection', Journal of General Virology, 81 889-894 (2000) [C1]
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2000 |
Gruarin P, Ulliers D, Thorne RF, Alessio M, 'Methionine 156 in the immunodominant domain on CD36 contributes to define the epitope recognized by the NL07 MoAb', Molecular and Cellular Biochemistry, 214 89-95 (2000) [C1]
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1998 |
Gruarin P, Sitia R, Thorne RF, Burns GF, Alessio M, 'CD36 is a ditopic glycoprotein with both transmembrane domains implicated in intracellular transport.', MOLECULAR BIOLOGY OF THE CELL, 9 456A-456A (1998) |
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1998 |
Bates RC, Elith CA, Thorne RF, Burns GF, 'Engagement of Variant CD44 confers resistance to anti-integrin antibody-mediated apoptosis in a colon carcinoma cell line', Cell Adhesion and Communication, 6 (1) 21-38 (1998) [C1]
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1998 |
Shafren DR, Dorahy DJ, Thorne RF, Kinoshita T, Barry RD, Burns GF, 'Antibody binding to individual short consensus repeats of decay-accelerating factor enhances enterovirus cell attachment and infectivity', The Journal of Immunology, 160 2318-2323 (1998) [C1]
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1997 |
Thorne RF, Meldrum CJ, Harris SJ, Dorahy DJ, Shafren DR, Berndt MC, et al., 'CD36 forms covalently associated dimers and multimers in platelets and transfected COS-7 cells', BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 240 812-818 (1997)
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1997 |
Dorahy DJ, Thorne RF, Fecondo JV, Burns GF, 'Stimulation of platelet activation and aggregation by a carboxyl-terminal peptide from thrombospondin binding to the integrin-associated protein receptor', JOURNAL OF BIOLOGICAL CHEMISTRY, 272 1323-1330 (1997)
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1997 |
Radford KJ, Thorne RF, Hersey P, 'Regulation of tumor cell motility and migration by CD63 in a human melanoma cell line', JOURNAL OF IMMUNOLOGY, 158 3353-3358 (1997)
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1996 |
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1989 |
SMART YC, STEVENSON KL, THORNE RF, THOMAS WD, HSU LH, BURTON RC, 'EXPRESSION OF NATURAL-KILLER (NK) CELL-SPECIFIC ALLOANTIGENS ON A MOUSE NK-LIKE CELL-LINE', IMMUNOLOGY AND CELL BIOLOGY, 67 239-242 (1989)
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