title: Hypoxia-induced SM22α in A549 cells activates the IGF1R/PI3K/Akt pathway, conferring cellular resistance against chemo- and radiation therapy.
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.
authors.affiliation: Department of Radiation Biology, Korea Atomic Energy Research Institute, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: Tae Rim
authors.initials: TR
authors.lastname: Kim
authors.forename: Eun Wie
authors.initials: EW
authors.lastname: Cho
authors.forename: Sang Gi
authors.initials: SG
authors.lastname: Paik
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005720:Gamma Rays; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000532:radiotherapy; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011836:Radiation Tolerance; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt