[WS8-1] 低酸素下でがん性代謝が確立される分子機構
When our body is exposed to hypoxic condition, we regulate metabolism, respiration, and erythropoiesis to adapt to the condition. Hypoxia-Inducible Factor (HIF) plays a central role in this process. Pyruvate dehydrogenase (PDH) is an enzyme which catalyzes the production of acetyl CoA from pyruvate. PDH consists of five subunits; E1α, E1β, E2, E3 and E3BP. Under hypoxic condition, HIF induces PDH kinase and promotes the phosphorylation of PDH-E1α to inhibit its activity. This pathway leads to the energetic conversion in hypoxia: from oxidative phosphorylation to glycolysis. In addition, we identified a new machinery to switch the metabolic status under prolonged hypoxic condition.
When breast cancer cell line was cultured in prolonged hypoxia, PDH-E1β is downregulated and the PDH activity is repressed. Further, downregulation of PDH-E1β was sustained after reoxygenation, which contributed to the aerobic glycolysis in cancer cells. Furthermore, knockdown (KD) of PDH-E1β created the aerobic glycolysis status, indicating that reduction of PDH activity plays a critical role on metabolic switching. Importantly, KD of PDH in cancer cells inhibited its growth even though they exhibit typical cancer metabolism. I would like to discuss a possible connection between the tumor metabolism and malignant phenotype of cancer cells, hoping to extend this notion to the study of microbiology.
When breast cancer cell line was cultured in prolonged hypoxia, PDH-E1β is downregulated and the PDH activity is repressed. Further, downregulation of PDH-E1β was sustained after reoxygenation, which contributed to the aerobic glycolysis in cancer cells. Furthermore, knockdown (KD) of PDH-E1β created the aerobic glycolysis status, indicating that reduction of PDH activity plays a critical role on metabolic switching. Importantly, KD of PDH in cancer cells inhibited its growth even though they exhibit typical cancer metabolism. I would like to discuss a possible connection between the tumor metabolism and malignant phenotype of cancer cells, hoping to extend this notion to the study of microbiology.