Hypoxia-induced IL-32 beta increases glycolysis in breast cancer cells

Abstract

IL-32 beta 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-32 beta is regulated by hypoxia was examined. Hypoxic conditions and a mimetic chemical CoCl2 enhanced IL-32 beta production. When cells were treated with various inhibitors of ROS generation to prevent hypoxia-induced ROS function, IL-32 beta production was suppressed by both NADPH coddase and mitochondrial ROS inhibitors. IL-32 beta translocated to the mitochondria under hypoxic conditions, where it was associated with mitochondrial biogenesis. Thus, whether hypoxia-induced IL-32 beta is associated with oxidative phosphorylation (OXPHOS) or glycolysis was examined. Glycolysis under aerobic and anaerobic conditions is impaired in IL-32 beta-depleted cells, and the hypoxia-induced IL-32 beta increased glycolysis through activation of lactate dehydrogenase. Src is also known to increase lactate dehydrogenase activity, and the hypoxia-induced IL-32 beta was found to stimulate Src activation by inhibiting the dephosphorylation of Src. These findings revealed that a hypoxia-ROS-IL-32 beta-Src-glycolysis pathway is associated with the regulation of cancer cell metabolism. (C) 2014 Elsevier Ireland Ltd. All rights reserved.