Ricerc@Sapienza

Epidermal Growth Factor Receptor (EGFR) is a cell surface protein with tyrosine kinase activity, and a major effector of extracellular signals promoting cell growth and survival, as well as developmental tissue differentiation. EGFR is also considered a proto-oncogene, since its aberrant/constitutive activation is responsible for cancer cell growth and invasive properties; furthermore, its upregulation leads to resistance to targeted therapies in human tumors. Due to its major impact in cell function, EGFR is subject to several regulatory mechanisms, at transcriptional, post-transcriptional, and post-translational levels. Moreover, a range of EGFR-interacting proteins controls EGFR activation, trafficking and intracellular signaling. Moreover, was recently found that specific cell surface co-receptors, as for example Neuropilins, play a major role in EGFR regulation, with potential relevance for cancer therapy. Intriguingly, Neuropilin-1 (Nrp1) has also been found to control the internalization of microRNAs (miRNAs) exchanged via the extracellular space (and circulating plasma), which are thereby translocated into the cytoplasm of Nrp1-expressing cells for the regulation of targeted transcripts. This novel function could represent an important mechanism of EGFR regulation, since multiple players of this signaling pathway are targeted by miRNAs. In sum, our project aims at elucidating novel mechanisms regulating EGFR signaling, via the uptake and internalization of circulating miRNAs.