We study in the team the involvement of the Met receptor tyrosine kinase and its signalling network in tumorigenesis. We demonstrated that Met is regulated by proteolytic cleavages controlling for instance the survival/apoptosis balance. We search as well to decipher the integration of the Met signalling at the transcriptional level directly involved in regulation of biological responses. Finally, we took advantage of the Met cleavages and its pro-apoptotic properties to develop original diagnostic and therapeutic strategies.

 

The deregulation of the receptor tyrosine kinase Met is associated with tumorigenesis and metastatic progression. It is now well established that proteolytic fragments of receptor tyrosine kinase (RTK) are important actors of their signalling. In this context, we have shown that Met cleavages by caspases and secretases control the survival/apoptosis balance and the half-life of the receptor. These original regulations of Met could be involved in tumorigenesis.

Although, the intracellular signalling network induced by Met is well cartographied, its integration at the transcriptional level is not described. We demonstrated that the transcription factors PEA3 are relays of the Met signalling. Here again, we search to understand the involvement of the transcriptional regulation in tumorigenesis induced by Met.

Finally, our works on the regulation of the survival/apoptosis balance led us to study the tumor suppressors often mutated in cancers. Our objective is to restore their expression to rescue sensitivity of tumoral cells to cell death. We search notably to inhibit NMD (nonsense-mediated mRNA decay) involved in degradation of tumor suppressors carrying nonsense mutations.

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