Hollande Laboratory: Molecular Mechanisms of Tumour Progression

Research Overview

The main focus of our work is to characterise signalling pathways that specify the role of tumour-initiating cells in cancer progression towards the metastatic stage, and to determine the respective contributions of intrinsic programs and of extrinsic/micro-environmental cues in the control of these signalling events. We also aim to characterise the molecular mechanisms underlying the phenotypic plasticity of cancer cells, and to understand how this plasticity affects the response of tumour-initiating cells to anticancer treatments.

Our research aims to dissect the molecular mechanisms that drive metastatic progression, to identify markers or early prognosis and to improve therapeutic efficiency by characterising cancer cells that resist current treatments and identifying novel approaches to target them.

Our interest is in solid tumours with a primary focus on colorectal cancer, a major public health issue and one of the main causes of cancer-related death in Australia and worldwide.

A broad array of experimental models are used in the team, including live and static cell imaging, flow cytometry, genome-wide analysis, transgenic and xenografted mice models, as well as ex vivo analysis of human tumour samples.

Staff

Dr Christina Molck (PhD), Post-doctoral Research Fellow (Danish Cancer Foundation)
Dr Sophie Paquet-Fifield (PhD), Post-doctoral Research Fellow (NH&MRC)
Ms Laura Marie Failla, Research Assistant
Ms Yan (Doris) Qin, PhD Student
Dr Adityas Purnianto (MD), Masters Student
Dr Corina Behrenbruch (MBBS), PhD Student

photo of Hollande lab personnel

Collaborators

National

Prof Mathias Ernst/Dr. Michael Buchert - Olivia Newton-John Cancer Research Institute (ONJCRI)
Dr. Erica Sloan - Monash Institute of Pharmaceutical Sciences, Monash University
Prof Alexander Heriot, Prof Robert Ramsey, Peter Mc Callum Cancer Centre, Melbourne
Dr Melissa Davis, Prof Edmund Crampin, Systems Biology Laboratory, The University of Melbourne
Dr Davide Ferrari, School of Mathematics and Statistics, The University of Melbourne
Prof Andrew Hill, Department of Biochemistry and Genetics, La Trobe University, Melbourne
Dr Kara Perrow, School of Biological Sciences, University of Wollongong, NSW.

International

Dr Julie Pannequin/Dr Jean Marc Pascussi, Institute of Functional Genomics, Montpellier, France
Dr. Serge Roche, CNRS Research Centre in Macromolecular Biochemistry (CRBM), Montpellier, France
Assoc Prof Sergei Rodin, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
Prof Jean-Paul Thiery, A*STAR Institute of Molecular and Cellular Biology, Singapore

Funding

National Health and Medical Research Council of Australia (NHMRC) Project grant: " Role of claudin-2 on the development of colorectal cancer metastases and their resistance to treatment"
NH&MRC Project grant "Establishing and validating a new therapeutic target for colon and stomach cancer"
NH&MRC Project grant "Novel Therapeutics for Colon Cancer treatment"
The University of Melbourne Department of Pathology

Research Publications

See a complete list of Fred Hollande's publications.

  • Aeson Chang, Corina Kim-Fuchs, Caroline P Le, Frederic Hollande, Erica K Sloan. Neural Regulation of Pancreatic Cancer: A Novel Target for Intervention. Cancers 2015; Jul 17;7(3): 1292-312. doi: 10.3390/cancers7030838.
  • Aeson Chang, Corina Kim-Fuchs, Caroline P. Le, Frederic Hollande, Erica K. Sloan * Alexandre David, Françoise Macari, Younas El-houfi, Galina Boldina, Hao Xu, Samer El-Khoury, Jérémy Ollier, Laura Yazdani, Ivan Bièche, Guanqun Zheng, Noémie Legrand, Damien Paulet, Stéphanie Durrieu, Anders Byström, Stephane Delbecq, Bruno lapeyre, Luc Bauchet, Julie Pannequin, Frederic Hollande, Tao Pan, Martin Teichmann, Stephan Vagner, Armelle Choquet, and Dominique Joubert. TRM6/61 connects PKCα with translational control through tRNAiMet stabilization: impact on tumorigenesis. Oncogene 2015 Aug 3. doi: 10.1038/onc.2015.244.
  • Benjamin B Williams, Niall C Tebbutt, Michael Buchert, Tracy L Putoczki, Karen Doggett, Shisan Bao, Cameron N Johnstone, Frederick Masson, Frederic Hollande, Antony W Burgess, Andrew M Scott, Matthias Ernst, and Joan K Heath. Glycoprotein A33 deficiency: a new model of impaired intestinal epithelial barrier function and inflammatory disease. Dis Model Mech 2015 Aug 1;8(8): 805-15.
  • Arsic N., Gadea G., Lagerqvist EL., Busson M., Cahuzac N., Brock C., Hollande F., Gire V., Pannequin J. and Roux P. The p53 Isoform D133p53b Promotes Cancer Stem Cell Potential. Stem Cell Reports 2015 http://dx.doi.org/10.1016/j.stemcr.2015.02.001
  • Breuker C, Planque C, Nault JC, Couchy G, Zucman-Rossi J, Evrard A, Kantar J, Chevet E, Bioulac-Sage P, Ramos J, Assenat E, Joubert D, Pannequin J, Hollande F, Pascussi JM. Characterization of a novel PXR isoform with potential dominant-negative properties. J Hepatol 2014 Sep;61(3): 609-16.
  • Paul Daniel, Gulay Filiz, Daniel V. Brown, Frédéric Hollande, Michael Gonzales, Giovanna D’Abaco, Nikos Papalexis, Wayne A. Phillips, Jordane Malaterre, Robert G. Ramsay, Theo Mantamadiotis. Selective CREB-dependent cyclin expression mediated by the PI3K and MAPK pathways regulates glioma cell proliferation. Oncogenesis 2014 Jun 30;3:e108. doi: 10.1038/oncsis.2014.21.
  • Corina Kim-Fuchs, Caroline P. Le, Matthew A. Pimentel, David Shackleford, Davide Ferrari, Eliane Angst, Frédéric Hollande, Erica K. Sloan. Chronic stress accelerates pancreatic cancer growth and invasion:  A critical role for beta-adrenergic signaling in the pancreatic microenvironment. Brain, Behavior, and Immunity 2014; Aug;40: 40-7.
  • Lapierre M, Bonnet S, Bascoul-Mollevi C, Ait-Arsa I, Jalaguier S, Del Rio M, Plateroti M, Roepman P, Ychou M, Pannequin J, Hollande F, Parker M and Cavailles V. The transcriptional coregulator RIP140 increases APC gene expression and controls intestinal homeostasis and tumorigenesis. J Clin Invest 2014 May 1;124(5): 1899-913.
  • Naudin C, Sirvent A, Leroy C, Simon V, Pannequin J, Bourgaux JF, Robert B, Hollande F and Roche S. SLAP displays tumor suppression function in colorectal cancer via destabilization of the SRC substrate EPHA2. Nature Communications 2014 Jan 24;5: 3159. doi: 10.1038/ncomms4159.
  • Bonnans C, Flacelière M, Grillet F, Dantec C, Desvignes JP, Pannequin J, Severac D, Dubois E, Bibeau F, Escriou V, Crespy P, Journot L, Hollande F* and Joubert D*. Essential requirement for beta-arrestin2 in mouse intestinal tumors with elevated Wnt signaling. (*Joint supervising authors). Proc Natl Acad Sci U S A 2012 Feb 21;109(8): 3047-52.
  • Schumacher MA, Donnelly JM, Engevik AC, Xiao C, Yang L, Kenny S, Varro A, Hollande F, Samuelson L and Zavros Y. Gastric Sonic Hedgehog Acts as a Macrophage Chemoattractant During the Development of the Immune Response to Helicobacter pylori. Infection. Gastroenterology. 2012 May;142(5): 1150-1159.e6.
  • Buchert M., Turksen K. and Hollande F. Methods to examine tight junction physiology in cancer stem cells: TEER, paracellular permeability, and dilution potential measurements. Stem Cell Rev 2012 Sep;8(3): 1030-4.
  • Hollande F, Joubert D. [Mitotic spindle and asymmetric stem cell division. ] Med Sci (Paris) 2010 Dec;26(12): 1027-1030. (French)
  • Xiao C, Ogle SA, Schumacher MA, Schilling N, Tokhunts RA, Orr-Asman MA, Miller ML, Robbins DJ, Hollande F, and Zavros Y. Hedgehog Signaling Regulates E-cadherin Expression for the Maintenance of the Actin Cytoskeleton and Tight-Junctions. Am J Physiol Gastrointest Liver Physiol 2010;299(6): G1252-65.
  • Raynal C, Pascussi JM, Leguelinel G, Breuker C, Kantar J, Lallemant B, Poujol S, Joubert D, Hollande F, Lumbroso S, Brouillet JP and Evrard A.  Pregnane X Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation. Molecular Cancer 2010;Mar 2; 9:46.
  • Hollande F., Pannequin J., and Joubert D. The long road to colorectal cancer therapy: searching for the right signals. Drug Resistance Updates 2010; Feb-Apr;13(1-2): 44-56.
  • Buchert M, Papin M, Bonnans C, Darido C, Raye WS, Garambois V, Pélegrin A, Bourgaux JF, Pannequin J, Joubert D, and Hollande F.  Symplekin promotes tumorigenicity by upregulating claudin-2 expression. Proc. Nat. Acad Sci USA 2010 Feb 9;107(6): 2628-33.

Research Projects



Faculty Research Themes

Cancer

School Research Themes

Cancer, Molecular Mechanisms of Disease, Cell Signalling



Key Contact

For further information about this research, please contact Associate Professor Fred Hollande

Department / Centre

Pathology