Ricerc@Sapienza

Autophagy is a degradative pathway playing a pivotal role in ensuring cellular homeostasis and stress response. On the last years we have demonstrated that the epithelial splice variant of fibroblast growth factor receptor 2 (FGFR2b) triggers both differentiation and autophagy, while the aberrant expression of the mesenchymal FGFR2c isoform in epithelial context induces impaired differentiation, EMT and tumorigenic features. More recently we found that FGFR2c also inhibit autophagy in human keratinocytes, impacting on the step of the autophagosome formation. In addition, silencing experiments of depletion of ESRP1, responsible for FGFR2 splicing and consequent FGFR2b expression, indicated that the altered splicing and the isoform switching from FGFR2b to FGFR2c underlie the inhibition of autophagy.
On the light of these recent evidences, in this project we plan: i) to identify the signaling pathways downstream FGFR2c responsible for the receptor-mediated inhibition of the autophagic process; ii) to establish if and how the repression of the autophagic process induced by FGFR2c play a role in receptor-mediated induction of EMT and tumorigenic features; iii) to look for possible key molecular hubs placed at the crossroad between autophagy and EMT. Our possible findings would significantly help to the identification of multiple molecular events regulating both the autophagic process and pathological EMT, contributing to the advancement of knowledge of the complex mechanisms leading to tumorigenesis.