Cell/cell and cell/matrix adhesion in the regulation of tumour-initiating cells
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Our lab is interested in the characterisation of signalling pathways that are differentially activated in Cancer Stem Cells (CSCs) from colorectal cancer, and to determine how the effects of intrinsic and environmental factors combine to regulate these pathways. We aim to characterise these regulators using integrated in vivo models of tumour progression and treatment response.
Among extrinsic regulators of cell phenotype, protein complexes involved in direct contacts between tumour and neighbouring cells have been shown to play an instrumental role in controlling the phenotype of CSCs. Claudin-2, an adhesion protein that is overexpressed in primary and metastatic human colorectal cancer (CRC), exerts tumour-promoting activities in vitro, and our results support the hypothesis that claudin-2 regulates self-renewal, a characteristic phenotypic trait of TICs. We are exploring the molecular mechanisms underlying this effect and analysing the regulatory role of claudin-2 on metastasis development and tumour relapse, two other processes where TIC involvement has been demonstrated.
In addition, extracellular matrix (ECM) proteins have emerged as important regulators of tumour progression and epithelial to mesenchyme transition (EMT), a program that has been shown to promote stemness characteristics in cancer cells. We are exploring the relationship between stemness and EMT during metastasis development, and we are particularly interested in the role of laminins in this process and in the impact of this family of proteins on the cancer stem cell phenotype.
Dr Sophie Paquet-Fifield (PhD), Post-doctoral Research fellow (NH&MRC)
Ms. Laura Marie Failla, Research Assistant
Ms Yan (Doris) Qin, PhD student
A/Prof Mathias Ernst/Dr. Michael Buchert - Olivia Newton-John Cancer Research Institute (ONJCRI)
Dr. Erica Sloan - Monash Institute of Pharmaceutical Sciences, Monash University
Professor Andrew Hill, Department of Biochemistry and Genetics, La Trobe University, Melbourne
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
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"
University of Melbourne Department of Pathology.
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