【摘 要】
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Tumor hypoxia is associated with cancer progression, but the hypoxia signaling mechanism remains largely unclear.Here, we show that Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/PO
【机 构】
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Department of Pharmacology, College of Pharmaceutical Sciences, Cyrus Tang Hematology Center, Affili
【出 处】
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江苏省药理学会青年工作委员会成立大会暨药理学科青年科技创新学术研讨会
论文部分内容阅读
Tumor hypoxia is associated with cancer progression, but the hypoxia signaling mechanism remains largely unclear.Here, we show that Nucleus accumbens-1 (NAC1), a nuclear factor belonging to the BTB/POZ gene family, is required for hypoxic induction of glycolysis and suppression of mitochondrial respiration that reduces oxygen consumption and inhibits the ROS production, and promotes cancer cells survival in hypoxia.We fotmd that NAC1 mediates metabolic switch in hypoxia through activating transcription of pyruvate dehydrogenase kinase 3 (PDK3), thereby inhibiting pyruvate dehydrogenase (PDH) and attenuating pyruvate into mitochondrial oxidation.Forced expression of PDK3 in hypoxia NAC 1 absent cells rescues these cells from hypoxia-induced apoptosis.Furthermore, we show that over-expression of NAC1 correlates with PDH inactivation in ovarian cancer tissues and that NAC1 short-hairpin RNA (shRNA)-expression xenograft tumors are decreased in size, increased in apoptosis and metabolically changed.Our findings not only reveal a previously unrecognized function of NAC1 and its impact on tumor development, but also identify a novel metabolic regulator that may be exploited as a potential target for cancer prevention.
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