The small molecule SI113 hinders epithelial‐to‐mesenchymal transition and subverts cytoskeletal organization in human cancer cells

摘要: The small molecule SI113 is an inhibitor of the kinase activity SGK1, a key biological regulator acting on PI3K/mTOR signal transduction pathway. Several studies demonstrate that this compound able to strongly restrain cancer growth in vitro and vivo, alone or associative antineoplastic treatments, being elicit autophagic response, either cytotoxic cytoprotective. To elucidate more exhaustively molecular mechanisms targeted by SI113, we performed activity-based protein profiling (ABPP) proteomic analysis using enrichment procedure. This technique allowed identification via mass spectrometry novel targets compound, most them involved functions concerning cell motility cytoskeletal architecture. Using glioblastoma multiforme, hepatocarcinoma colorectal carcinoma line, recognized inhibitory effect migration, invading, epithelial-to-mesenchymal transition. In addition, these cells, when exposed showed remarkable subversion architecture characterized F-actin destabilization, phospho-FAK delocalization, tubulin depolimerization. These results were definitely concordant attributing role hindering malignancy and, due its negligible vivo toxicity, can sustain performing Phase I clinical trial employ drug therapy.