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. SM22α is an actin-binding protein found in smooth muscle, fibroblasts, and some epithelium. We demonstrate that SM22α is induced in A549 non-small cell lung carcinoma cells by hypoxia and its overexpression increased chemo- and radiation-resistance. Hypoxia-mediated induction of SM22α expression is hypoxia-inducible factor-independent. Moreover, SM22α overexpression enhances tumor cell growth and activates the IGF1R/PI3K/Akt pathway via direct interaction with IGF1Rβ. Our results suggest SM22α as a novel regulator of hypoxic survival pathway of A549 NSCLC cells.Structured summary of protein interactionsIGFR1 Betaphysically interacts with SM22 alpha by anti bait coimmunoprecipitation (View Interaction: 1, 2)

► SM22α is induced in A549 non-small cell lung carcinoma cells by hypoxia.
► SM22α overexpression increased chemo- and radiation-resistance of A549 NSCLC cells.
► Hypoxia-mediated induction of SM22α expression is hypoxia-inducible factor-independent.
► SM22α overexpression activates the IGF1R/PI3K/Akt pathway via direct interaction with IGF1Rβ.
► SM22α is suggested as a novel regulator of hypoxic survival pathway of A549 NSCLC cells.