FCHSD2 controls oncogenic ERK1/2 signaling by regulating endocytic trafficking in non-small-cell lung cancer

摘要: Non-small-cell lung cancer (NSCLC) is the major cause of cancer deaths. The evolution of transformed NSCLC cells into metastatic tumors is, in part, driven by altered intracellular signaling downstream of receptor tyrosine kinases (RTKs). The surface levels and activity of RTKs are governed mainly through clathrin-mediated endocytosis (CME), endosomal recycling or degradation. We recently discovered that oncogenic signaling downstream of RTKs can reciprocally regulate CME and endocytic trafficking by creating feedback loops and that some of these mechanisms for crosstalk between signaling and endocytosis appear to be specific for, or co-opted by cancer cells to enhance tumor progression. We previously identified that FCHSD2 (FCH/F-BAR and double SH3 domain-containing protein) has a cancer-cell specific function in regulating CME downstream of ERK1/2 in NSCLC cells. It is now critical to further …