My main research interest is in the role of growth factor receptor signalling and trafficking in tumour metastasis.
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. *Co-last authors. PMID: 24790222
A direct role for Met endocytosis in tumorigenesis. Nat Cell Biol (2011) 13(7):827-37. PMID: 2164298
We study compartmental signalling of a molecule called 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.
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 c-Met in promoting this process of metastasis.
Receptorsare 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.
Key finding: 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).
The Role of PI3K in Met Driven Cancer: A Recap. Hervieu A, Kermorgant S Front Mol Biosci (2018) 5(2) 86
Understanding and targeting Met signalling in bladder cancer Badreldin W, Powles T, Menard L et al. ANNALS OF ONCOLOGY (2017) 28(11)
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
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
PI3K class I and mTOR regulate distinct steps in Met dependent tumorigenesis Hervieu A, Kermorgant S MOLECULAR CANCER THERAPEUTICS (2015) 14(11)
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
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
Postdoctoral Researchers in this group
Dr Sara Farrah Heuss
Mr Bakhouche Bakhouche, Ms Brynna Hoggard
Clinical Research Fellows
Dr Waleed Badreldin, Dr Georgina Wood
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.