title: Hypoxia-induced IL-32β increases glycolysis in breast cancer cells.
abstract: IL-32β is highly expressed and increases the migration and invasion of gastric, lung, and breast cancer cells. Since IL-32 enhances VEGF production under hypoxic conditions, whether IL-32β is regulated by hypoxia was examined. Hypoxic conditions and a mimetic chemical CoCl2 enhanced IL-32β production. When cells were treated with various inhibitors of ROS generation to prevent hypoxia-induced ROS function, IL-32β production was suppressed by both NADPH oxidase and mitochondrial ROS inhibitors. IL-32β translocated to the mitochondria under hypoxic conditions, where it was associated with mitochondrial biogenesis. Thus, whether hypoxia-induced IL-32β is associated with oxidative phosphorylation (OXPHOS) or glycolysis was examined. Glycolysis under aerobic and anaerobic conditions is impaired in IL-32β-depleted cells, and the hypoxia-induced IL-32β increased glycolysis through activation of lactate dehydrogenase. Src is also known to increase lactate dehydrogenase activity, and the hypoxia-induced IL-32β was found to stimulate Src activation by inhibiting the dephosphorylation of Src. These findings revealed that a hypoxia-ROS-IL-32β-Src-glycolysis pathway is associated with the regulation of cancer cell metabolism.
authors.affiliation: Department of Biosystems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Biosystems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Sunyi
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biosystems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Ae Lee
authors.initials: AL
authors.lastname: Jeong
authors.affiliation: Department of Biosystems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Sora
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Biosystems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Hye In
authors.initials: HI
authors.lastname: Ka
authors.affiliation: Department of Biosystems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Biosystems, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Myung Sok
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry, Kangwon National University, Chuncheon 200-701, Republic of Korea.
authors.forename: Jeong-Hyung
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biosystems, Sookmyung Women's University, Seoul 140-742, Republic of Korea. Electronic address: yyang@sm.ac.kr.
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004734:Energy Metabolism; D005260:Female; D006019:Glycolysis; D006801:Humans; D000860:Hypoxia; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C496971:IL32 protein, human; D007378:Interleukins; D034741:RNA, Small Interfering; D019061:src-Family Kinases
keywords: Glycolysis; Hypoxia; Interleukin-32; Mitochondrial biogenesis; OXPHOS