title: Irradiation of Epithelial Carcinoma Cells Upregulates Calcium-Binding Proteins That Promote Survival under Hypoxic Conditions.
abstract: Hypoxia is thought to promote tumor radio-resistance via effects on gene expression in cancer cells that modulate their metabolism, proliferation, and DNA repair pathways to enhance survival. Here we demonstrate for the first time that under hypoxic condition A431 epithelial carcinoma cells exhibit increased viability when exposed to low-dose γ-irradiation, indicating that radiotherapy can promote tumor cell survival when oxygen supply is limited. When assessed using iTRAQ quantitative proteomics and Western blotting, irradiated tumor cells were observed to significantly up-regulate the expression of calcium-binding proteins CALM1, CALU, and RCN1, suggesting important roles for these mediators in promoting tumor cell survival during hypoxia. Accordingly, shRNA-knockdown of CALM1, CALU, and RCN1 expression reduced hypoxic tumor cell resistance to low-dose radiation and increased apoptosis. These data indicate that γ-irradiation of hypoxic tumor cells induces up-regulation of calcium-binding proteins that promote cancer cell survival and may limit the efficacy of radiotherapy in the clinic.
authors: School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, Singapore 637551.|BGI-Shenzhen , Yantian District Beishan Industrial Zone 11th building, Shenzhen, China 518083.
authors: Yan
authors: Y
authors: Ren
authors: National Cancer Centre Singapore , Department of Radiation Oncology, 11 Hospital Drive, Singapore 169610.
authors: Kheng Wei
authors: KW
authors: Yeoh
authors: School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, Singapore 637551.
authors: Piliang
authors: P
authors: Hao
authors: National Cancer Centre Singapore , Division of Medical Sciences, 11 Hospital Drive, Singapore 169610.
authors: Oi Lian
authors: OL
authors: Kon
authors: School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, Singapore 637551.
authors: Siu Kwan
authors: SK
authors: Sze
mesh_terms: D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000528:radiation effects*; D002147:Calmodulin / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004847:Epithelial Cells / Q000473:pathology; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D000860:Hypoxia; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D040901:Proteomics / Q000379:methods; D047368:Tumor Burden / Q000528:radiation effects*; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: C000607143:CALM1 protein, human; C510527:CALU protein, human; D002135:Calcium-Binding Proteins; D002147:Calmodulin; C000597745:RCN1 protein, human
keywords: LC−MS/MS; calcium signaling; cancer; hypoxia; iTRAQ; proteomics; radiotherapy resistance