Hypoxia-induced IL-32β increases glycolysis in breast cancer cells. Issue 2 (28th January 2015)

• Record Type: Journal Article
• Authors: Park, Jeong Su; Lee, Sunyi; Jeong, Ae Lee; Han, Sora; Ka, Hye In; Lim, Jong-Seok; Lee, Myung Sok; Yoon, Do-Young; Lee, Jeong-Hyung; Yang, Young
• Is Part Of: Cancer letters. Volume 356:Issue 2(2015)Part B
• Page Start: 800
• Page End: 808
• Publication Date: 2015-01-28
• Subjects: ECAR extracellular acidification rate -- HIF-1 hypoxia inducible factor-1 -- IL-32 interleukin-32 -- LDH-A lactate dehydrogenase A -- OCR oxygen consumption rate -- OXPHOS oxidative phosphorylation -- PDK1 pyruvate dehydrogenase kinase -- PFKFB4 fructose-2, 6-bisphosphatase 4 -- PKM2 pyruvate kinase M2 -- PP2A protein phosphatase 2A -- PPP pentose phosphate pathway -- ROS reactive oxygen species; Interleukin-32 -- Hypoxia -- Mitochondrial biogenesis -- OXPHOS -- Glycolysis; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2014.10.030
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Hypoxia-induced ROS increase IL-32β expression. IL-32β enhances glycolytic pathway through increase of LDH activity under hypoxic conditions. Inhibition of hypoxia-induced IL-32β impairs tumor cell growth. IL-32β increases Src activity via protecting the dephosphorylation of Src by PP2A. 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.