Recent works revealed that receptors transmit information not only from the cell surface but also from inside the cells, on endosomes. The aim is to understand how c-Met receptor transmits information inside the cell and why intracellular c-Met receptor activity is required for optimal cell behaviour. This project will apply engineering technology for the automatic imaging, quantification, and modeling of c-Met “endosomal signalling” in human breast and lung cells and tissues, combined to biochemistry and functional assays including cell migration, proliferation and survival. Novel technologies measuring and modeling receptor endosomal signaling will be generated, enhancing basic knowledge of receptor signalling.
Trusolino L, Bertotti A, Comoglio PM. MET signalling: principles and functions in development, organ regeneration and cancer. Nat Rev Mol Cell Biol. 2010 11:834-48
Kermorgant S and Parker PJ. Receptor trafficking controls weak signal delivery: a strategy employed by c-Met for STAT3 nuclear accumulation J Cell Biol 18:855-63
Joffre C, Barrow R, Ménard L, Calleja V, Hart IR and Kermorgant S. A direct role for Met endocytosis in tumorigenesis Nature Cell Biology 13:827-37
Barrow-McGee R, Kermorgant S. Met Endosomal Signalling: In the right place, at the right time. Int J Biochem Cell Biol 2014, 49:69-74;
Ménard L, Parker PJ, Kermorgant S. Receptor Tyrosine Kinase c-Met controls the cytoskeleton from different endosomes via different pathways. Nature Communications 2014, 5:3907