Professor Stéphanie Kermorgant
Group Leader
Overview
We study the role of growth factor receptor signalling and intracellular trafficking (movement inside cells) in tumour growth and metastasis in the view of improving cancer therapy.
Team
Luke Bossons
PhD Student
Dr Katia Bouchekioua-Bouzaghou
Postdoctoral Researcher
Dr Malgorzata Maksymowicz-Trivedi
Postdoctoral Researcher
Andrea Vinaga
PhD Student
Research
Most solid cancers start as a small lump of abnormal cells (a tumour) that divide in an uncontrolled fashion. As primary tumours grow, some cancer cells can detach, move away and, eventually, colonise another part of the body. This aggressive process is called metastasis and is the major cause of cancer treatment failure and death. Our research focuses on understanding the mechanisms of molecule called c-Met in promoting this process of metastasis.
c-Met is overexpressed or mutated in a large number of tumours and has emerged as a major target for cancer therapy. c-Met is a tyrosine kinase receptor (RTK). Together with the protein that binds to it: its ligand, Hepatocyte Growth Factor (HGF), they are key players in tumour metastasis. They affect cell adhesion, migration, invasion, metalloproteinase activation and angiogenesis. Drugs against c-Met are being designed and some are being tested in patients in clinical trials.
Receptors such as c-Met are normally present at the surface of transformed cells in the tumour mass, where they transmit information (signals) from the outside to the inside of the cell in order to change its behaviour (divide/don’t divide; move/don’t move). However, receptors can enter cells (endocytosis) and recently have been found to transmit signals from within the cell. This is a new scientific concept that changes our understanding of how receptors function.
We study the signalling of c-Met in relation to its endosomal trafficking (how it is moved around the cell in vesicles) and the effects on tumour cell migration and invasion in vitro and in vivo. We use confocal microscopy, live imaging, biochemistry, trafficking / internalisation assays, functional assays, and in vivo tumorigenesis assays. We investigate the clinical relevance of our findings on patient samples through collaboration with clinicians. We work on breast, pancreatic, lung and ovarian cancer. We have reported that c-Met mutants found in cancer patients are oncogenic not only because they are highly activated but also because they signal on endosomes. We have shown that c-Met transmit distinct signalling pathways from different endosomes including a novel endosome we recently discovered, the “Autophagy Related Endomembrane”.
We anticipate that a better understanding of the molecular biology of intracellular c-Met will lead to improved cancer treatment.
Key Publications
A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration. Science Signaling (2020) 13 (637): eaba8627. DOI: 10.1126/scisignal.aba8627
Beta 1-integrin- c-Met cooperation reveals an inside-in survival signalling on Autophagy Related Endomembranes. Nature Communications (2016) 7:11942. PMID: 27336951
Receptor Tyrosine Kinase c-Met controls the cytoskeleton from different endosomes via different pathways. Nature Communications (2014) 5:3907. PMID: 24835487
Distinct c-Met Activation Mechanisms Induce Cell Rounding or Invasion Through Pathways Involving Integrins, RhoA, and Hip1. J Cell Sci (2014) 127:1938-52. PMID: 24790222
A direct role for Met endocytosis in tumorigenesis. Nat Cell Biol (2011) 13(7):827-37. PMID: 2164298
See recent publicationsMajor Funding
- 2018-2021- Medical Research Council, Project Grant, Unravelling c-Met signalling from autophagic endomembranes, £502,856.32
- 2018-2019- OCTIMET Oncology, Unravelling the Mode of Action of Proprietary MET Kinase Inhibitors on the Immune System and Innovative Biomarker Identification to Accelerate Valorisation of these Inhibitors, £327,480
Other Activities
- Norwegian Cancer Society Grants External Review Panel Chair
- Management Committee Member of London Interdisciplinary Biosciences Consortium (LIDo)
- Academic Editor of the journal Cells
- Reviewer Editor of the journal Frontiers in Molecular Bioscience
- Reviewer Editor of the journal Frontiers Oncology
Biography
I completed my PhD with Dr. Thérèse Lehy at the French National Institute of Health and Medicine (INSERM) and Paris VII University, France, in 1999.
Between 2000 and 2005, I performed postdoctoral studies with Professor Peter J Parker at the Cancer Research UK London Research Institute.
I joined the Centre for Tumour Biology at the Barts Cancer Institute in May 2005, as a Lecturer. Thanks to a “Medical Research Council New Investigator Award” and funding from the “Barts and the London Charitable Foundation”, I set up my research group “Spatial Signalling”, which is investigating the role of growth factor receptor signalling and trafficking in tumour metastasis.
Related News
New insight into how a faulty protein drives lung cancer gives clues to why some therapies fail
The findings could help explain why cancer drugs that target the molecule MET work for some people but not others.
General News 15 June 2023
Unravelling the circuitry that controls cancer growth and spread
Research reveals novel insights into the molecular circuitry controlling cancer cell growth and spread. The findings highlight new pathways involved in these key processes of cancer progression that may represent targets for therapies.
General News 23 June 2020