Dr Stéphanie Kermorgant

PhD
Reader in Cellular Oncology
Group Leader
Research Focus

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.

Key Publications

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

Major 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 Member

  • Irish Cancer Society Biochemical Research Fellowship Review Panel Member

  • Management Committee Member of  London Interdisciplinary Biosciences Consortium (LIDo) 

  • Evaluator for the WHRI-ACADEMY fellowship programme 2nd Call for Proposals

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.

Other Activities
  • Norwegian Cancer Society Grants External Review Panel Member

  • Irish Cancer Society Biochemical Research Fellowship Review Panel Member

  • Management Committee Member of  London Interdisciplinary Biosciences Consortium (LIDo) 

  • Evaluator for the WHRI-ACADEMY fellowship programme 2nd Call for Proposals

Major 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
Recent Publications

The Role of PI3K in Met Driven Cancer: A Recap. Hervieu A, Kermorgant S Front Mol Biosci (2018) 5(2) 86
https://www.ncbi.nlm.nih.gov/pubmed/30406111

Understanding and targeting Met signalling in bladder cancer Badreldin W, Powles T, Menard L et al. ANNALS OF ONCOLOGY (2017) 28(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000411324000057&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Corrigendum: Beta 1-integrin-c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes. Barrow-McGee R, Kishi N, Joffre C et al. Nat Commun (2016) 7(1) 12392-12392
https://www.ncbi.nlm.nih.gov/pubmed/27447817

Beta 1-integrin–c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes BRENNAN CH Nature Communications (2016) 7(1) 11942-11942

Beta 1-integrin–c-Met cooperation reveals an inside-in survival signalling on autophagy-related endomembranes Barrow-McGee R, Kishi N, Joffre C et al. Nature Communications (2016) 7(1) 11942-11942

Desmoglein 3 regulates membrane trafficking of cadherins, an implication in cell-cell adhesion Mofta H, Dias K, Hoque Apu E et al. Cell Adhesion & Migration (2016) (1)

Desmoglein 3 regulates membrane trafficking of cadherins, an implication in cell-cell adhesion. Moftah H, Dias K, Apu EH et al. Cell Adhesion and Migration (1) 1-22
http://www.ncbi.nlm.nih.gov/pubmed/27254775

PI3K class I and mTOR regulate distinct steps in Met dependent tumorigenesis Hervieu A, Kermorgant S MOLECULAR CANCER THERAPEUTICS (2015) 14(11)
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000358159200066&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

The clinical and functional significance of c-Met in breast cancer: a review. Ho-Yen CM, Jones JL, Kermorgant S Breast Cancer Res (2015) 17(2) 52
https://www.ncbi.nlm.nih.gov/pubmed/25887320

Role for Desmoglein 3 in regulating E-cadherin trafficking Moftah H, Diaz K, Kermorgant S et al. JOURNAL OF INVESTIGATIVE DERMATOLOGY (2014) 134(11) S29-S29
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000340352100166&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

For additional publications, please click here
Team

Postdoctoral Researchers in this group
Dr Marie Nollet, Dr Bakhouche Bakhouche

PhD Students
Ms Brynna Hoggard, Mr Alejandro Noval

Clinical Research Fellows
Dr Waleed Badreldin, Dr Georgina Wood

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.