Ricerc@Sapienza

Autophagy is an auto-digestion process crucial to ensure maintenance of cellular homeostasis. On the last years we have demonstrated that the epithelial splicing variant of the fibroblast growth factor receptor 2 (FGFR2b) triggers autophagy in human keratinocytes and that this event is required for receptor-dependent differentiation (Belleudi et al., 2014, Belleudi et al., 2015, Nanni et al., 2018). On the other hand, our recent reports indicated that the aberrant expression of the FGFR2c mesenchymal isoform in the epithelial context induces impaired differentiation, epithelial-mesenchymal transition (EMT) and tumorigenic features (Ranieri et al., 2015, Ranieri et al., 2016, Ranieri et al., 2018). These published results coupled to few preliminary observations encourage us to suppose a potential role of the aberrant expression of the oncogenic FGFR2c splicing variant in the deregulation of the negative crosstalk between autophagy and EMT in epithelial cells. To evaluate the impact of FGFR2 altered splicing on this crosstalk, we plan to assess if the EMT triggered by the FGFR2c aberrant expression and signaling in epithelial context could be the consequence of a deregulated autophagy in a negative crosstalk. To this aim we propose: i) to verify if FGFR2c could impact on autophagy and if the possible dysfunction of the autophagic process could play a role in receptor-mediated induction of EMT and tumorigenic features; ii) to identify the molecular mechanisms at the crossroad between FGFR2c-mediated autophagy and EMT. The expected results may contribute to clarify the molecular interplay linking autophagy and pathological EMT, which could be triggered by the aberrant expression of the oncogenic FGFR2c splicing receptor variant in the epithelial context, leading to carcinogenesis.