Abstract
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.
Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / metabolism
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Carcinoma, Non-Small-Cell Lung / radiotherapy
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Cell Hypoxia / drug effects
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Cell Hypoxia / genetics
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Cell Hypoxia / physiology*
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Cell Hypoxia / radiation effects
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Cell Line, Tumor
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Drug Resistance, Neoplasm
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Gamma Rays
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Humans
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Lung Neoplasms / drug therapy
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Lung Neoplasms / metabolism
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Lung Neoplasms / radiotherapy
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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Muscle Proteins / genetics
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Muscle Proteins / metabolism*
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Phosphatidylinositol 3-Kinases / metabolism*
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Proto-Oncogene Proteins c-akt / metabolism*
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Radiation Tolerance
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Receptor, IGF Type 1 / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / radiation effects
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Up-Regulation
Substances
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Antineoplastic Agents
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Microfilament Proteins
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Muscle Proteins
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transgelin
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Phosphatidylinositol 3-Kinases
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Receptor, IGF Type 1
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Proto-Oncogene Proteins c-akt