Hypoxia-induced SM22α in A549 cells activates the IGF1R/PI3K/Akt pathway, conferring cellular resistance against chemo- and radiation therapy

Chemo- or radiation-resistance in tumors caused by hypoxia often undermines efficacy of cancer therapy. Thus, therapies that overcome cellular resistance during hypoxia are necessary. SM22 alpha is an actin-binding protein found in smooth muscle, fibroblasts, and some epithelium. We demonstrate that SM22 alpha is induced in A549 non-small cell lung carcinoma cells by hypoxia and its overexpression increased chemo- and radiation-resistance. Hypoxia-mediated induction of SM22 alpha expression is hypoxia-inducible factor-independent. Moreover, SM22 alpha overexpression enhances tumor cell growth and activates the IGF1R/PI3K/Akt pathway via direct interaction with IGF1R beta. Our results suggest SM22 alpha as a novel regulator of hypoxic survival pathway of A549 NSCLC cells. Structured summary of protein interactions: IGFR1 Beta physically interacts with SM22 alpha by anti bait coimmunoprecipitation (View Interaction: 1, 2) (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.