Dr Stéphanie Kermorgant

PhD
Centre: Tumour Biology
Senior Lecturer
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My main research interest is in the role of growth factor receptor signalling and trafficking in tumour metastasis.

Research Details

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 a molecule called c-Met in promoting this process of metastasis.

Receptors 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.

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.

Our Research

In an effort to develop new therapeutic strategies, we aim to understand how c-Met transmits signals from inside the cell and how this tells the cell to move away from the primary tumour.

We study compartmental 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.

Key findings

We discovered that c-Met mutants found in cancer patients are oncogenic not only because they are highly activated but also because they signal on the endosome. Thus blocking endocytosis impairs cell transformation and migration in vitro and in vivo (Joffre et al, Nat Cell Biol, 2011).

More recently, we reported that in invasive basal-like breast cancer cells, not only is c-Met endocytosis important but the endosome from which c-Met signals plays a major role in determining cell behaviour, including migration (Menard et al, Nat Com 2014).

Profile

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.

Funding

2015 Pancreatic Cancer UK PhD Studentship
£102,000
2014  Pancreatic Cancer Research Fund "Understanding and targeting c-Met endosomal signalling in pancreatic cancer”
£180,000

2014

Breast Cancer Campaign "Understanding how breast cancer cells start to migrate"
£20,000

2013

Rosetree Trust "The importance of the location of c-MET, a promising target in breast cancer"
£10,000

2012

Medical Research Council MRC Centenary Award
£56,431

2012

Barts And The London Charity Understanding and targeting c-Met pathway in Trastuzumab resistant breast Cancer
£184,882
2011 Medical Research Council PhD Studentship
£75,000

2009

Breast Cancer Campaign Project Grant: "Spatio-temporal c-met signalling"
£187,368

2009

British Lung Foundation Project Grant: "c-Met in NSCLC-taking Functional Genomics into a Clinical Context"
£143,328

2008

Medical Research Council PhD Studentship
£71,700
2007 Medical Research Council New Investigator Award
£300,000

Key Publications

Beta 1-integrin- c-Met cooperation reveals an inside-in survival signalling on Autophagy Related Endomembranes. Barrow-McGee R, Kishi N, Joffre C, Ménard L, Hervieu A, Bakhouche BA, Rivero AJN, Mai A, Gutierr CG, Robert-Masson L, Iturrioz X, Hulit J, Brennan C, Hart IR, Parker PJ, Ivaska J, Kermorgant S. (2016) Nature Communications, PMID: 27336951

Receptor Tyrosine Kinase c-Met controls the cytoskeleton from different endosomes via different pathways. Ménard L, Parker PJ, Kermorgant S. (2014) Nature Communications, 5:3907. PMID: 24835487

Distinct c-Met Activation Mechanisms Induce Cell Rounding or Invasion Through Pathways Involving Integrins, RhoA, and Hip1. Mai A, Muharram G, Barrow R, Baghirov H, Rantala J, Kermorgant S*, Ivaska J*. (2014) J Cell Sci, 127:1938-52. *Co-last authors. PMID: 24790222

A direct role for Met endocytosis in tumorigenesis. Joffre C, Barrow R, Ménard L, Calleja V, Hart IR, Kermorgant S. (2011) Nat Cell Biol, 13(7):827-37. doi: 10.1038/ncb2257. PMID: 2164298

 


Further Publications

For additional publications, please click here.


My main research interest is in the role of growth factor receptor signalling and trafficking in tumour metastasis.

External Activities

  • Member of:
    • Biochem Soc
    • BACR
  • Evaluator for the WHRI-ACADEMY fellowship programme 2nd Call for Proposals

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