Professor Hubert Hondermarck

Professor Hubert Hondermarck

Professor

School of Biomedical Sciences and Pharmacy (Medical Biochemistry)

Career Summary

Biography

Hubert Hondermarck is Professor of Medical Biochemistry. He obtained a PhD in neurobiochemistry at the University of Lille (1990, France) and was a post-doc at the University of California Irvine (1990-1993) where he investigated the mechanisms of neuronal cell differentiation using proteomics. He was appointed on an academic position at the University of Lille (1993) to work on signaling of breast cancer cell growth and metastasis. He became full Professor in 1998 and a member of the "Institut Universitaire de France" (Chair of cancer proteomics) in 2002. He founded a research unit of the French Institute of Health and Medical Research (U908 INSERM, growth factor signaling and functional proteomics in breast cancer) and directed it for 10 years. In 2011, he moved to the University of Newcastle to start a new program on the function of neurotrophic growth factors and the impact of the nervous system in cancer initiation and progression.

Hbert Hondermarck is an elected member of the Board of Directors of the Human Proteome Organization (HUPO). He is also in the following Editorial Boards: Molecular and Cellular Proteomics (ASBMB), Proteomics Clinical Applications (Wiley), Open Cancer Journal (Bentham) and Frontiers in Endocrinology (Frontiers Media). He was President of the French proteomics Society (SFEAP)  from 2005 to 2007.

Research Expertise
Hubert Hondermarck's group works on the crosstalk between nerves and cancer cells, and its impact on tumour progression. Until recently it was thought that neurons were not actively involved in cancer. However, recent evidence in prostate and breast cancers, including from our group (Pundavela et al Am J Pathol. 2014, Pundavela et al Mol Oncol 2015, Jobling et al Cancer Res. 2015), have shown that nerves promote tumour progression and that denervation can suppress both the development of the primary tumor and the outburst of metastases.

The objective of our research is to identify the molecular mediators of the crosstalk between nerves and cancer cells that may constitute new and innovative biomarkers and therapeutic targets. Our methodologies include the analysis of human tumour samples, cell cultures, in vivo experiments, proteomics and mass spectrometry analysis. We work in collaboration with neurobiologists, pathologists, clinicians and private companies to translate the results of our research into practical outcomes in oncology. Scientific production: 84 PubMed referenced articles on cancer cell biology and proteomics http://www.ncbi.nlm.nih.gov/pubmed?term=hondermarck, and 2 internationally issued patents in collaboration with biopharmaceutical companies.

Most recent publications

Dun MD, Chalkley RJ, Faulkner S, Keene S, Avery-Kiejda K, Scott RJ, Falkenby LG, Cairns MJ, Larsen MR, Bradshaw RA, Hondermarck
H. Proteotranscriptomic profiling of 231-BR breast cancer cells: identification of potential biomarkers and therapeutic targets for brain metastasis. Mol Cell Proteomics. 2015 Jun 3. [Epub ahead of print]

Pundavela J, Roselli S, Faulkner S, Attia J, Scott RJ, Thorne RF, Bradshaw RA, Walker MM, Jobling P, Hondermarck H. Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer. Molecular Oncol. 2015 May 14. [Epub ahead of print]

Roselli S, Pundavela J, Demont Y, Faulkner S, Sheridan K, AttiaJ, Jiang CC, Zhang XD, Walker MM, Hondermarck H. Sortilin is associated with breast cancer aggressiveness and contributes to tumour cell adhesion and invasion. Oncotarget 2015, 6(12):10473-86.

Faulkner, S., Dun, M.D., Hondermarck, H. Proteogenomics: emergence and promise. Cell Mol Life Sci. 2015 72(:953-7. Jobling P, Pundavela J, Oliverira SMR, Roselli S, Walker MM, Hondermarck H. Nerve-cancer cell crosstalk: a novel promoter of tumor progression. Cancer Res. 2015, 75, 1-5.

Pundavela J, Demont Y, Jobling P, Lincz LF, Roselli S, Thorne RF, Bond D, Bradshaw RA, Walker MM, Hondermarck H. ProNGF correlates with Gleason score and is a potential driver of nerve infiltration in prostate cancer. Am J Pathol. 2014. 184, 3156-62.

Teaching Expertise
Biochemistry, proteomics, cancer biology, bioinformatics.

Administrative Expertise
Head of the Discipline of Medical Biochemistry (Faculty of Health and Medicine).



Qualifications

  • PhD (Life Sciences & Health), University of Lille - France

Keywords

  • Cancer biology
  • Cellular and molecular biology
  • Growth factors
  • Proteomics
  • Translational cancer research

Fields of Research

Code Description Percentage
110106 Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) 40
111201 Cancer Cell Biology 60

Professional Experience

UON Appointment

Title Organisation / Department
Professor University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (28 outputs)

Year Citation Altmetrics Link
2015 Blanckaert V, Kerviel V, Lépinay A, Joubert-Durigneux V, Hondermarck H, Chénais B, 'Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1.', Int J Oncol, 46 2649-2655 (2015)
DOI 10.3892/ijo.2015.2936
2015 Faulkner S, Dun MD, Hondermarck H, 'Proteogenomics: emergence and promise.', Cell Mol Life Sci, 72 953-957 (2015)
DOI 10.1007/s00018-015-1837-y
Co-authors Matt Dun
2015 Faulkner S, Dun MD, Hondermarck H, 'Proteogenomics: Emergence and promise', Cellular and Molecular Life Sciences, 72 953-957 (2015)

Proteogenomics, or the integration of proteomics with genomics and transcriptomics, is emerging as the next step towards a unified understanding of cellular functions. Looking glo... [more]

Proteogenomics, or the integration of proteomics with genomics and transcriptomics, is emerging as the next step towards a unified understanding of cellular functions. Looking globally and simultaneously at gene structure, RNA expression, protein synthesis and posttranslational modifications have become technically feasible and offer a new perspective to molecular processes. Recent publications have highlighted the value of proteogenomics in oncology for defining the molecular signature of human tumors, and translation to other areas of biomedicine and life sciences is anticipated. This minireview will discuss recent developments, challenges and perspectives in proteogenomics.

DOI 10.1007/s00018-015-1837-y
Citations Scopus - 1
Co-authors Matt Dun
2015 Faulkner S, Dun MD, Hondermarck H, 'Proteogenomics: Emergence and promise', Cellular and Molecular Life Sciences, 72 953-957 (2015)

Proteogenomics, or the integration of proteomics with genomics and transcriptomics, is emerging as the next step towards a unified understanding of cellular functions. Looking glo... [more]

Proteogenomics, or the integration of proteomics with genomics and transcriptomics, is emerging as the next step towards a unified understanding of cellular functions. Looking globally and simultaneously at gene structure, RNA expression, protein synthesis and posttranslational modifications have become technically feasible and offer a new perspective to molecular processes. Recent publications have highlighted the value of proteogenomics in oncology for defining the molecular signature of human tumors, and translation to other areas of biomedicine and life sciences is anticipated. This minireview will discuss recent developments, challenges and perspectives in proteogenomics.

DOI 10.1007/s00018-015-1837-y
Citations Scopus - 1
Co-authors Matt Dun
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, (2015)

Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a co... [more]

Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p=0.0003). In invasive breast cancers, the presence of nerve fibers was observed in 15% of lymph node negative tumors and 28% of lymph node positive tumors (p=0.0031), indicating a relationship with the metastatic potential. In addition, there was an association between the presence of nerve fibers and the expression of nerve growth factor (NGF) in cancer cells (p=0.0001). Invitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti-NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered.

DOI 10.1016/j.molonc.2015.05.001
Co-authors Marjorie Walker, Phillip Jobling, John Attia, Rodney Scott, Rick Thorne, John Forbes
2015 Dun MD, Chalkley RJ, Faulkner S, Keene S, Avery-Kiejda K, Scott RJ, et al., 'Proteotranscriptomic Profiling of 231-BR Breast Cancer Cells: Identification of Potential Biomarkers and Therapeutic Targets for Brain Metastasis.', Mol Cell Proteomics, (2015)
DOI 10.1074/mcp.M114.046110
Co-authors Matt Dun, Murray Cairns, Kelly Kiejda
2015 Jobling P, Pundavela J, Oliveira SM, Roselli S, Walker MM, Hondermarck H, 'Nerve-Cancer Cell Cross-talk: A Novel Promoter of Tumor Progression.', Cancer Res, 75 1777-1781 (2015)
DOI 10.1158/0008-5472.CAN-14-3180
Co-authors Phillip Jobling, Marjorie Walker
2015 Bradshaw RA, Pundavela J, Biarc J, Chalkley RJ, Burlingame AL, Hondermarck H, 'NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling', Advances in Biological Regulation, 58 16-27 (2015)

Nerve growth factor (NGF) and its precursor (proNGF) are primarily considered as regulators of neuronal function that induce their responses via the tyrosine kinase receptor TrkA ... [more]

Nerve growth factor (NGF) and its precursor (proNGF) are primarily considered as regulators of neuronal function that induce their responses via the tyrosine kinase receptor TrkA and the pan-neurotrophin receptor p75NTR. It has been generally held that NGF exerts its effects primarily through TrkA, inducing a cascade of tyrosine kinase-initiated responses, while proNGF binds more strongly to p75NTR. When this latter entity interacts with a third receptor, sortilin, apoptotic responses are induced in contrast to the survival/differentiation associated with the other two. Recent studies have outlined portions of the downstream phosphoproteome of TrkA in the neuronal PC12 cells and have clarified the contribution of individual docking sites in the TrkA endodomain. The patterns observed showed a similarity with the profile induced by the epidermal growth factor receptor, which is extensively associated with oncogenesis. Indeed, as with other neurotrophic factors, the distribution of TrkA and p75NTR is not limited to neuronal tissue, thus providing an array of targets outside the nervous systems. One such source is breast cancer cells, in which NGF and proNGF stimulate breast cancer cell survival/growth and enhance cell invasion, respectively. This latter activity is exerted via TrkA (as opposed to p75NTR) in conjunction with sortilin. Another tissue overexpressing proNGF is prostate cancer and here the ability of cancer cells to induce neuritogenesis has been implicated in cancer progression. These studies show that the non-neuronal functions of proNGF/NGF are likely integrated with their neuronal activities and point to the clinical utility of these growth factors and their receptors as biomarkers and therapeutic targets for metastasis and cancer pain.

DOI 10.1016/j.jbior.2014.11.003
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 : CMLS, (2015)
DOI 10.1007/s00018-015-1955-6
Co-authors Lisa Lincz, Rick Thorne
2015 Roselli S, Pundavela J, Demont Y, Faulkner S, Keene S, Attia J, et al., 'Sortilin is associated with breast cancer aggressiveness and contributes to tumor cell adhesion and invasion.', Oncotarget, 6 10473-10486 (2015)
Co-authors John Attia, Marjorie Walker, Xu Zhang
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, tB = 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.

DOI 10.1016/j.ajpath.2014.08.009
Citations Scopus - 2Web of Science - 2
Co-authors Rick Thorne, Lisa Lincz, Marjorie Walker, Phillip Jobling
2014 Bradshaw RA, Pundavela J, Biarc J, Chalkley RJ, Burlingame AL, Hondermarck H, 'NGF and ProNGF: Regulation of neuronal and neoplastic responses through receptor signaling', Advances in Biological Regulation, (2014)

Nerve growth factor (NGF) and its precursor (proNGF) are primarily considered as regulators of neuronal function that induce their responses via the tyrosine kinase receptor TrkA ... [more]

Nerve growth factor (NGF) and its precursor (proNGF) are primarily considered as regulators of neuronal function that induce their responses via the tyrosine kinase receptor TrkA and the pan-neurotrophin receptor p75NTR. It has been generally held that NGF exerts its effects primarily through TrkA, inducing a cascade of tyrosine kinase-initiated responses, while proNGF binds more strongly to p75NTR. When this latter entity interacts with a third receptor, sortilin, apoptotic responses are induced in contrast to the survival/differentiation associated with the other two. Recent studies have outlined portions of the downstream phosphoproteome of TrkA in the neuronal PC12 cells and have clarified the contribution of individual docking sites in the TrkA endodomain. The patterns observed showed a similarity with the profile induced by the epidermal growth factor receptor, which is extensively associated with oncogenesis. Indeed, as with other neurotrophic factors, the distribution of TrkA and p75NTR is not limited to neuronal tissue, thus providing an array of targets outside the nervous systems. One such source is breast cancer cells, in which NGF and proNGF stimulate breast cancer cell survival/growth and enhance cell invasion, respectively. This latter activity is exerted via TrkA (as opposed to p75NTR) in conjunction with sortilin. Another tissue overexpressing proNGF is prostate cancer and here the ability of cancer cells to induce neuritogenesis has been implicated in cancer progression. These studies show that the non-neuronal functions of proNGF/NGF are likely integrated with their neuronal activities and point to the clinical utility of these growth factors and their receptors as biomarkers and therapeutic targets for metastasis and cancer pain.

DOI 10.1016/j.jbior.2014.11.003
2013 Bailly F, Toillon R-A, Tomavo O, Jouy N, Hondermarck H, Cotelle P, 'Antiproliferative and apoptotic effects of the oxidative dimerization product of methyl caffeate on human breast cancer cells', BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 23 574-578 (2013) [C1]
DOI 10.1016/j.bmcl.2012.11.009
Citations Scopus - 2Web of Science - 2
2012 Demont Y, Corbet C, Page A, Ataman-Onal Y, Choquet-Kastylevsky G, Fliniaux I, et al., 'Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein', Journal of Biological Chemistry, 287 1923-1931 (2012) [C1]
Citations Scopus - 13Web of Science - 11
2011 Wilmet J-P, Tastet C, Desruelles E, Ziental-Gelus N, Blanckaert V, Hondermarck H, Le Bourhis X, 'Proteome changes induced by overexpression of the p75 neurotrophin receptor (p75(NTR)) in breast cancer cells', INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY, 55 801-809 (2011) [C1]
DOI 10.1387/ijdb.113345jw
Citations Scopus - 4Web of Science - 5
2011 Vanhecke E, Adriaenssens E, Verbeke S, Meignan S, Germain E, Berteaux N, et al., 'Brain-derived neurotrophic factor and neurotrophin-4/5 are expressed in breast cancer and can be targeted to inhibit tumor cell survival', Clinical Cancer Research, 17 1741-1752 (2011) [C1]

Purpose: Given that nerve growth factor has previously been shown to be involved in breast cancer progression, we have tested here the hypothesis that the other neurotrophins (NT)... [more]

Purpose: Given that nerve growth factor has previously been shown to be involved in breast cancer progression, we have tested here the hypothesis that the other neurotrophins (NT) are expressed and have an influence in breast tumor growth. Experimental Design: The expression of brain-derived neurotrophic factor (BDNF), NT-3 and NT-4/5, as well as the neurotrophin receptor p75 NTR, TrkB, and TrkC, was studied by RT-PCR, Western blotting, and immunohistochemistry in cell lines and tumor biopsies. The biological impacts of neurotrophins, and associated mechanisms, were analyzed in cell cultures and xenografted mice. Results: BDNF and NT-4/5 were expressed and secreted by breast cancer cells, and the use of blocking antibodies suggested an autocrine loop mediating cell resistance to apoptosis. The corresponding tyrosine kinase receptor TrkB was only rarely observed at full length, whereas the expression of TrkB-T1, lacking the kinase domain, as well as p75 NTR, were detected in all tested breast cancer cell lines and tumor biopsies. In contrast, NT-3 and TrkC were not detected. SiRNA against p75 NTR and TrkB-T1 abolished the antiapoptotic effect of BDNF and NT-4/5, whereas the pharmacological inhibitors K252a and PD98059 had no effect, suggesting the involvement of p75 NTR and TrkB-T1, but not kinase activities from Trks and MAPK. In xenografted mice, anti-BDNF, anti-NT-4/5, anti-p75 NTR, or anti-TrkB-T1 treatments resulted in tumor growth inhibition, characterized by an increase in cell apoptosis, but with no change in proliferation. Conclusion: BDNF and NT-4/5 contribute to breast cancer cell survival and can serve as prospective targets in attempts to inhibit tumor growth. ©2011 AACR.

DOI 10.1158/1078-0432.CCR-10-1890
Citations Scopus - 28
2010 Lagadec C, Romon R, Tastet C, Meignan S, Com E, Page A, et al., 'Ku86 is important for TrkA overexpression-induced breast cancer cell invasion', Proteomics - Clinical Applications, 4 580-590 (2010) [C1]

Purpose: We have recently shown that breast tumors express high levels of TrkA compared with normal breast tissues, with TrkA overexpression enhancing breast cancer cell invasion ... [more]

Purpose: We have recently shown that breast tumors express high levels of TrkA compared with normal breast tissues, with TrkA overexpression enhancing breast cancer cell invasion in vitro and metastasis in animal models. In this study, we tried to identify molecules involved in TrkA overexpression-mediated biological effects in breast cancer cells. Experimental design: We used a proteomic-based approach to identify proteins involved in TrkA overexpression-stimulated invasion of MDA-MB-231 breast cancer cells. Proteins from control and TrkA overexpressing cells were separated using a cup-loading two-dimensional electrophoresis system before MALDI and LC-MS/MS mass spectrometry analysis. Results: Among several putative regulated proteins, Ku86 was found increased in TrkA overexpressing cells. Moreover, Ku86 was co-immunoprecipitated with TrkA, suggesting the interaction of these two proteins in TrkA overexpressing cells. Interestingly, inhibition with small-interfering RNA and neutralizing antibodies showed that Ku86 was required for TrkAstimulated cell invasion. Conclusions and clinical relevance: These data allowed the identification of Ku86 as a new player involved in metastasis in breast cancer cells. Our findings suggest that TrkA and its down stream signaling pathways should be regarded as potential new targets for the development of future breast cancer therapy. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOI 10.1002/prca.200900148
Citations Scopus - 7
2010 Romon R, Adriaenssens E, Lagadec C, Germain E, Hondermarck H, Le Bourhis X, 'Nerve growth factor promotes breast cancer angiogenesis by activating multiple pathways', Molecular Cancer, 9 (2010) [C1]
DOI 10.1186/1476-4598-9-157
Citations Scopus - 39
2010 Le Bourhis X, Romon R, Hondermarck H, 'Role of endothelial progenitor cells in breast cancer angiogenesis: From fundamental research to clinical ramifications', Breast Cancer Research and Treatment, 120 17-24 (2010) [C1]

Blood vessel formation (neovascularization) in tumors can occur through two mechanisms: angiogenesis and vasculogenesis. Angiogenesis results from proliferation and sprouting of e... [more]

Blood vessel formation (neovascularization) in tumors can occur through two mechanisms: angiogenesis and vasculogenesis. Angiogenesis results from proliferation and sprouting of existing blood vessels close to the tumor, while vasculogenesis is believed to arise from recruitment of circulating cells, largely derived from the bone marrow, and de novo clonal formation of blood vessels from these cells. Increasing evidence in animal models indicate that bone marrow-derived endothelial precursor cells (EPC) can contribute to tumor angiogenesis. This review aims to collate existing literature and provide an overview on the current knowledge of EPC involvement in breast cancer angiogenesis. We also discuss recent attempts to use EPC as biomarker and therapeutic target in clinical trials. © 2009 Springer Science+Business Media, LLC.

DOI 10.1007/s10549-009-0686-5
Citations Scopus - 18
2010 Verbeke S, Meignan S, Lagadec C, Germain E, Hondermarck H, Adriaenssens E, Le Bourhis X, 'Overexpression of p75NTR increases survival of breast cancer cells through p21waf1 ', Cellular Signalling, 22 1864-1873 (2010) [C1]

The p75 neurotrophin receptor (p75NTR) plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation and proliferation. To eva... [more]

The p75 neurotrophin receptor (p75NTR) plays a critical role in various neuronal and non-neuronal cell types by regulating cell survival, differentiation and proliferation. To evaluate the influence of p75NTR in breast cancer development, we have established and characterized breast cancer cells which stably overexpress p75NTR. We showed that p75NTR overexpression per se promoted cell survival to apoptogens with a concomitant slowdown of cell growth. The pro-survival effect is associated with an increased expression of the inhibitor of apoptosis protein-1 (c-IAP1), a decrease of TRAIL-induced cleavage of PARP, procaspase 9 and procaspase 3, and a decrease of cytochrome C release from the mitochondria. The anti-proliferative effect is due to a cell accumulation in G0/G1, associated with a decrease of Rb phosphorylation and an increase of p21waf1. Interestingly, inhibition of p21waf1 with siRNA not only restores proliferation but also abolishes the pro-survival effect of p75NTR, indicating the key role of p21waf1 in the biological functions of p75NTR. Finally, using a SCID mice xenograft model, we showed that p75NTR overexpression favors tumor growth and strongly increases tumor resistance to anti-tumoral treatment.Together, our findings suggest that p75NTR overexpression in breast tumor cells could favor tumor survival and contribute to tumor resistance to drugs. This provides a rationale to consider p75NTR as a potential target for the future design of innovative therapeutic strategies. © 2010 Elsevier Inc.

DOI 10.1016/j.cellsig.2010.07.014
Citations Scopus - 14
2009 Collins BC, Lau TYK, O'Connor DP, Hondermarck H, 'Cancer proteomics - An evolving battlefield: Conference on cancer proteomics 2009: Mechanistic insights, technological advances & molecular medicine', EMBO Reports, 10 1202-1205 (2009) [E3]
DOI 10.1038/embor.2009.222
Citations Scopus - 7
2009 Joubel A, Chalkley RJ, Medzihradszky KF, Hondermarck H, Burlingame AL, 'Identification of new p53 acetylation sites in COS-1 cells', Molecular and Cellular Proteomics, 8 1167-1173 (2009) [C1]

The p53 tumor suppressor protein is a key regulator of cell cycle and death that is involved in many cell signaling pathways and is tightly regulated in mammalian cells. Post-tran... [more]

The p53 tumor suppressor protein is a key regulator of cell cycle and death that is involved in many cell signaling pathways and is tightly regulated in mammalian cells. Post-translational modifications of p53 have been investigated previously mainly using antibodies. In this study, utilizing LC-MS/MS analysis, we have characterized p53 protein from COS-1 cells. Several already known posttranslational modifications were observed, such as phosphorylation on serines 15, 33, 315, and 392 as well as acetylation on lysines 305, 370, 372, 373, 381, 382, and 386. Interestingly novel acetylation sites were identified at lysines 319 and 357. This study confirmed that p53 is a highly acetylated protein and revealed new acetylation sites that might aid the further understanding of p53 regulation. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI 10.1074/mcp.M800487-MCP200
Citations Scopus - 8
2009 Strande V, Canelle L, Tastet C, Burlet-Schiltz O, Monsarrat B, Hondermarck H, 'The proteome of the human breast cancer cell line MDA-MB-231: Analysis by LTQ-Orbitrap mass spectrometry', Proteomics - Clinical Applications, 3 41-50 (2009) [C1]

We have used a combination of SDS-PAGE and LTQ-Orbitrap MS to explore the proteome of the highly invasive MDA-MB-231 breast cancer cell line. Based on about 520 000 MS/MS spectra,... [more]

We have used a combination of SDS-PAGE and LTQ-Orbitrap MS to explore the proteome of the highly invasive MDA-MB-231 breast cancer cell line. Based on about 520 000 MS/MS spectra, a total of 3481 proteins were identified and subsequently classified according to their cellular distribution and molecular function. Interestingly, a large proportion of proteins (38%) were from cellular membranes and we were able to characterize numerous proteins involved in cancer initiation and progression such as the tumor suppressor p53 and the epidermal growth factor receptor. Together, this study represents the largest proteome database of breast cancer cells realized to date and demonstrates the value of using Orbitrap MS for deeper proteome analysis. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

DOI 10.1002/prca.200800083
Citations Scopus - 6
2009 Lagadec C, Meignan S, Adriaenssens E, Foveau B, Vanhecke E, Romon R, et al., 'TrkA overexpression enhances growth and metastasis of breast cancer cells', Oncogene, 28 1960-1970 (2009) [C1]

The Trk family of neurotrophin tyrosine kinase receptors is emerging as an important player in carcinogenic progression in non-neuronal tissues. Here, we show that breast tumors p... [more]

The Trk family of neurotrophin tyrosine kinase receptors is emerging as an important player in carcinogenic progression in non-neuronal tissues. Here, we show that breast tumors present high levels of TrkA and phospho-TrkA compared to normal breast tissues. To further evaluate the precise functions of TrkA overexpression in breast cancer development, we have performed a series of biological tests using breast cancer cells that stably overexpress TrkA. We show that (1) TrkA overexpression promoted cell growth, migration and invasion in vitro; (2) overexpression of TrkA per se conferred constitutive activation of its tyrosine kinase activity; (3) signal pathways including PI3K-Akt and ERK/p38 MAP kinases were activated by TrkA overexpression and were required for the maintenance of a more aggressive cellular phenotype; and (4) TrkA overexpression enhanced tumor growth, angiogenesis and metastasis of xenografted breast cancer cells in immunodeficient mice. Moreover, recovered metastatic cells from the lungs exhibited enhanced anoikis resistance that was abolished by the pharmacological inhibitor K252a, suggesting that TrkA-promoted breast tumor metastasis could be mediated at least in part by enhancing anoikis resistance. Together, these results provide the first direct evidence that TrkA overexpression enhances the tumorigenic properties of breast cancer cells and point to TrkA as a potential target in breast cancer therapy. © 2009 Macmillan Publishers Limited All rights reserved.

DOI 10.1038/onc.2009.61
Citations Scopus - 65
2008 Hondermarck H, Tastet C, Yazidi-Belkoura IE, Toillon R-A, Bourhis XL, 'Proteomics of breast cancer: The quest for markers and therapeutic targets', Journal of Proteome Research, 7 1403-1411 (2008) [C1]

Proteomics of breast cancer has already delivered significant data in terms of proteome profiling in addition to the identification of a few proteins of potential interest for dia... [more]

Proteomics of breast cancer has already delivered significant data in terms of proteome profiling in addition to the identification of a few proteins of potential interest for diagnosis and treatment. With more pathological and experimental situations being studied, it now enters into a new phase dominated by the concepts of deep proteome analysis and the definition of protein-protein interaction networks leading to mammary cell deregulation and cancer progression. Together, what could be called "Systems Proteomics", integrating with information from the genomics and the physiopathology, is clearly emerging to become the frame for future investigations. However, difficulties ahead should not be underestimated. First, the proteome is complex, and current tools are still far from providing a definitive solution for its exploration. Second, breast cancer is a multifactorial disease which is so diverse that a great deal of time and efforts will be necessary to define its associated proteome modifications and translate it into practical applications for the clinic. © 2008 American Chemical Society.

DOI 10.1021/pr700870c
Citations Scopus - 36
2008 Hondermarck H, 'Nerve Growth Factor: The Dark Side of the Icon', The American Journal of Pathology, 172 865-867 (2008) [C3]
DOI 10.2353/ajpath.2008.080008
2008 Adriaenssens E, Vanhecke E, Saule P, Mougel A, Page A, Romon R, et al., 'Nerve growth factor is a potential therapeutic target in breast cancer', Cancer Research, 68 346-351 (2008) [C1]

We show here that nerve growth factor (NGF), the prototypic neurotrophin, can be targeted in breast cancer to inhibit tumor cell proliferation, survival, and metastasis. Analysis ... [more]

We show here that nerve growth factor (NGF), the prototypic neurotrophin, can be targeted in breast cancer to inhibit tumor cell proliferation, survival, and metastasis. Analysis of a series of biopsies revealed widespread expression of NGF in the majority of human breast tumors, with anti-NGF immunoreactivity concentrated in the epithelial cancer cells. Moreover, immunodeficient mice xenografted with human breast cancer cells and treated with either anti-NGF antibodies or small interfering RNA against NGF displayed inhibited tumor growth and metastasis. Such treatments directed against NGF induced a decrease in cell proliferation with a concomitant increase in apoptosis of breast cancer cells and an inhibition of tumor angiogenesis. Together, these data indicate that targeting NGF in breast cancer may have therapeutic ramifications. ©2008 American Association for Cancer Research.

DOI 10.1158/0008-5472.CAN-07-1183
Citations Scopus - 66
2008 Berteaux N, Aptel N, Cathala G, Genton C, Coll J, Daccache A, et al., 'A novel H19 antisense RNA overexpressed in breast cancer contributes to paternal IGF2 expression', Molecular and Cellular Biology, 28 6731-6745 (2008) [C1]

The H19/IGFf2 locus belongs to a large imprinted domain located on human chromosome 11p15.5 (homologue to mouse distal chromosome 7). The H19 gene is expressed from the maternal a... [more]

The H19/IGFf2 locus belongs to a large imprinted domain located on human chromosome 11p15.5 (homologue to mouse distal chromosome 7). The H19 gene is expressed from the maternal allele, while IGF2 is paternally expressed. Natural antisense transcripts and intergenic transcription have been involved in many aspects of eukaryotic gene expression, including genomic imprinting and RNA interference. However, apart from the identification of some IGF2 antisense transcripts, few data are available on that topic at the H19/IGF2 locus. We identify here a novel transcriptional activity at both the human and the mouse H19/IGF2 imprinted loci. This activity occurs antisense to the H19 gene and has the potential to produce a single 120-kb transcript that we called the 91H RNA. This nuclear and short-lived RNA is not imprinted in mouse but is expressed predominantly from the maternal allele in both mice and humans within the H19 gene region. Moreover, the transcript is stabilized in breast cancer cells and overexpressed in human breast tumors. Finally, knockdown experiments showed that, in humans, 91H, rather than affecting H19 expression, regulates IGF2 expression in trans. Copyright © 2008, American Society for Microbiology. All Rights Reserved.

DOI 10.1128/MCB.02103-07
Citations Scopus - 49
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Review (1 outputs)

Year Citation Altmetrics Link
2012 Hondermarck H, 'Neurotrophins and their receptors in breast cancer', Cytokine & Growth Factor Reviews (2012) [C1]
Citations Scopus - 14Web of Science - 16

Conference (6 outputs)

Year Citation Altmetrics Link
2014 Dun MD, Chalkley RJ, Keene S, Bradshaw RA, Hondermarck H, 'Proteomics versus Transcriptomics for the Identification of Cancer Biomarkers: the Case of Brain-derived Metastatic Breast Cancer Cells', MOLECULAR & CELLULAR PROTEOMICS (2014) [E3]
Co-authors Matt Dun
2014 Faulkner S, Roselli S, Thorne RF, Scarlett CJ, Walker MM, Hondermarck H, 'PRONGF AND SORTILIN EXPRESSION AND FUNCTION IN PANCREATIC CANCER', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
Co-authors Rick Thorne, Marjorie Walker, C Scarlett
2014 Shargh VH, Hondermarck H, Liang M, 'MULTIFUNCTIONAL NANOMEDICINES BASED ON ALBUMIN FOR TARGETED BREAST CANCER THERAPY', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
Co-authors Roger Liang
2014 Oliveira SMR, Roselli S, Hondermarck H, Jobling P, 'PERIPHERAL NERVES ARE ASSOCIATED WITH SOME OVARIAN TUMOURS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
Co-authors Phillip Jobling
2013 Ahmed AF, De Bock CE, Sontag E, Hondermarck H, Thorne RF, 'The functional role of Fat1 cadherin in the differentiation and proliferation of SH-SY5Y neuroblastoma cells', -, Pokolbin, NSW, Australia (2013) [E3]
Co-authors Rick Thorne, Estelle Sontag
2012 Roselli SM, Moscato PA, Scott R, Hondermarck H, 'Breast cancer proteomics: Integrating the data with genomics and histology towards clinical applications', 18th Proteomics Symposium. Delegate Handbook, Lorne, Vic (2012) [E3]
Co-authors Rodney Scott, Pablo Moscato
Show 3 more conferences
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Grants and Funding

Summary

Number of grants 15
Total funding $2,607,338

Click on a grant title below to expand the full details for that specific grant.


20152 grants / $696,250

High resolution fourier transform mass spectrometry platform for the discovery of novel cancer biomarkers and drug targets using label-free and isobaric-tagged approaches for quantitative proteomics.$500,000

Funding body: Cancer Institute NSW

Funding body Cancer Institute NSW
Project Team Professor Xu Dong Zhang, Doctor Matt Dun, Professor Jennifer Martin, Professor Hubert Hondermarck, Laureate Professor John Aitken, Doctor Nikki Verrills, Doctor Pradeep Tanwar, Professor Rodney Scott, Professor Maria Kavallaris, Dr Darren Saunders
Scheme Research Equipment Grant
Role Investigator
Funding Start 2015
Funding Finish 2016
GNo G1500599
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

High resolution fourier transform mass spectrometry platform for the discovery of novel cancer biomarkers and drug targets using label-free and isobaric-tagged approaches for quantitative proteomics.$196,250

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Professor Xu Dong Zhang, Doctor Matt Dun, Professor Jennifer Martin, Professor Hubert Hondermarck, Laureate Professor John Aitken, Doctor Nikki Verrills, Doctor Pradeep Tanwar, Professor Rodney Scott, Professor Maria Kavallaris, Dr Darren Saunders
Scheme Equipment Grant
Role Investigator
Funding Start 2015
Funding Finish 2015
GNo G1500935
Type Of Funding Internal
Category INTE
UON Y

20144 grants / $499,487

High Throughput Image Capture Platform for Translational Cancer Research$282,614

Funding body: Cancer Institute NSW

Funding body Cancer Institute NSW
Project Team Conjoint Professor Stephen Ackland, Professor Rodney Scott, Professor John Forbes, Professor Xu Dong Zhang, Professor Marjorie Walker, Professor Hubert Hondermarck, Doctor Craig Gedye, Doctor Rick Thorne, Mr Loui Rassam, Doctor Stephen Braye
Scheme Research Equipment Grant
Role Investigator
Funding Start 2014
Funding Finish 2014
GNo G1400626
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

Visualisation of microparticles for development of biomarkers and targeted drug delivery mechanisms$125,199

Funding body: Cancer Institute NSW

Funding body Cancer Institute NSW
Project Team Doctor Christopher Scarlett, Doctor Kathryn Skelding, Doctor Jude Weidenhofer, Doctor Matt Dun, Doctor Kelly Kiejda, Professor Adam McCluskey, Ms Elham Sadeqzadeh, Professor Hubert Hondermarck, Doctor Rick Thorne, Professor Rodney Scott
Scheme Research Equipment Grant
Role Investigator
Funding Start 2014
Funding Finish 2014
GNo G1400627
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

JuLI Stage $71,674

Funding body: NHMRC (National Health & Medical Research Council)

Prostate Cancer: A new protein for improving diagnosis, prognosis and treatment$20,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Severine Roselli, Professor Hubert Hondermarck
Scheme Project Grant
Role Investigator
Funding Start 2014
Funding Finish 2014
GNo G1401520
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

20134 grants / $361,096

Triple Quadrupole Mass Spectrometer with nano-infusion for targeted protein quantification$300,000

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Doctor Mark Baker, Laureate Professor John Aitken, Conjoint Professor Bogdan Dlugogorski, Professor Hubert Hondermarck
Scheme Equipment Grant
Role Investigator
Funding Start 2013
Funding Finish 2013
GNo G1200137
Type Of Funding Internal
Category INTE
UON Y

12th World Congress of the Human Proteome Organization (HUPO), Yokohama Japan, 14 - 18 September 2013$1,500

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding body University of Newcastle - Faculty of Health and Medicine
Project Team Professor Hubert Hondermarck
Scheme Travel Grant
Role Lead
Funding Start 2013
Funding Finish 2013
GNo G1300864
Type Of Funding Internal
Category INTE
UON Y

20124 grants / $494,694

High-Resolution Isoelectric Phosphoprotein Signalling System for Signalling Research, Biomarker Validation and Drug Development – Equipment Grant$143,394

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Rick Thorne, Professor Xu Dong Zhang, Professor Hubert Hondermarck, Conjoint Professor Stephen Ackland, Doctor Lisa Lincz, Doctor Jennette Sakoff, Emeritus Professor Leonie Ashman
Scheme Project Grant
Role Investigator
Funding Start 2012
Funding Finish 2012
GNo G1200555
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

Microscopic illumination system for advanced fluorescent protein technology$34,000

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Doctor Rick Thorne, Professor Xu Dong Zhang, Conjoint Associate Professor Murray Cairns, Doctor Nikki Verrills, Doctor Charles De Bock, Doctor Jude Weidenhofer, Doctor Severine Roselli, Doctor Kathryn Skelding, Emeritus Professor Leonie Ashman, Professor Hubert Hondermarck
Scheme Equipment Grant
Role Investigator
Funding Start 2012
Funding Finish 2012
GNo G1100983
Type Of Funding Other Public Sector - Commonwealth
Category 2OPC
UON Y

Does Ubiquitination control the altered expression of tetraspanin proteins in Breast Cancer?$25,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Jude Weidenhofer, Emeritus Professor Leonie Ashman, Professor Hubert Hondermarck
Scheme Project Grant
Role Investigator
Funding Start 2012
Funding Finish 2012
GNo G1200169
Type Of Funding Contract - Aust Non Government
Category 3AFC
UON Y

20111 grants / $555,811

Priority Research Centre for Cancer$555,811

Funding body: University of Newcastle

Funding body University of Newcastle
Project Team Conjoint Professor Stephen Ackland, Professor Xu Dong Zhang, Professor John Forbes, Emeritus Professor Leonie Ashman, Doctor Nikola Bowden, Professor Gordon Burns, Conjoint Professor Jim Denham, Professor Hubert Hondermarck, Doctor Lisa Lincz, Doctor Jennette Sakoff, Associate Professor Peter Stanwell, Doctor Rick Thorne, Doctor Nikki Verrills
Scheme Priority Research Centre
Role Investigator
Funding Start 2011
Funding Finish 2011
GNo G1101013
Type Of Funding Internal
Category INTE
UON Y
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Research Supervision

Number of supervisions

Completed2
Current10

Total current UON EFTSL

PhD1.9

Current Supervision

Commenced Level of Study Research Title / Program / Supervisor Type
2015 PhD The Role of mTOR Hyperactivation in the Pathogenesis of PCOS
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2015 PhD Investigating Novel Co-molecular Lesions of TP-53 in Serous Adeno Carcinomas and Their Role in DNA Damage
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2015 PhD Biomarkers for Circulating Ovarian Cancer Cells: A Prognostic and Therapeutic Approach
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2014 PhD ProNGF and its Receptors in Pancreatic Cancer and Melanoma
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Principal Supervisor
2014 PhD The Nerve-Cancer Connection: Tumour Innervation and Trophic Factors in Ovarian Cancer
Human Biology, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2014 PhD Role of mTOR signalling in Ovarian Cancer
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2014 PhD WNT Signaling in Uterine Cancer
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2013 PhD Multifunctional Nanomedicines Based on Albumin for Targeted Cancer Therapy
Pharmacy, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2013 PhD Role of Wnt Signalling in Testicular Morphogenesis and Carcinogenesis
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2013 PhD Role of Wnt Signalling in Endometrial Homeostasis and Cancer
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor

Past Supervision

Year Level of Study Research Title / Program / Supervisor Type
2015 PhD Role of FAT1 Cadherin in Neuronal Differentiation
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Co-Supervisor
2015 PhD ProNGF/NGF and Nerve Infiltration in Prostate and Breast Cancer
Medical Science, Faculty of Health and Medicine, The University of Newcastle
Principal Supervisor
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News

John Forbes

International spotlight on cancer research

October 23, 2013

Four of North America's leading cancer researchers will give keynote presentations at the international Translational Cancer Research Conference in Newcastle from tomorrow until Friday.

Professor Hubert Hondermarck

Position

Professor
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Focus area

Medical Biochemistry

Contact Details

Email hubert.hondermarck@newcastle.edu.au
Phone (02) 4921 8830
Fax (02) 4921 7903

Office

Room LS3-35
Building Life Sciences
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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