巴基斯坦卢比
脂肪酸合酶
甾醇调节元件结合蛋白
癌症研究
PI3K/AKT/mTOR通路
蛋白激酶B
癌细胞
细胞生长
化学
细胞生物学
生物
丙酮酸激酶
转录因子
癌症
脂质代谢
信号转导
糖酵解
内分泌学
生物化学
新陈代谢
基因
遗传学
作者
Ting Tao,Qiongli Su,Simeng Xu,Jun Deng,Sichun Zhou,Zhuang Yu,Yanjun Huang,Caimei He,Shanping He,Mei Peng,Berthold Hocher,Xiaoping Yang
摘要
Fatty acid synthase (FASN) catalyzing the terminal steps in the de novo biogenesis of fatty acids is correlated with low survival and high disease recurrence in patients with bladder cancer. Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels and provides a growth advantage to tumors. However, it is unclear whether the change of PKM2 has an effect on FASN and what is the mechanisms underlying. Here we describe a novel function of PKM2 in control of lipid metabolism by mediating transcriptional activation of FASN, showing the reduced expression of sterol regulatory element binding protein 1c (SREBP-1c). We first discovered that PKM2 physically interacts with the SREBP-1c using biochemical approaches, and downregulation of PKM2 reduced the expression of SREBP-1c by inactivating the AKT/mTOR signaling pathway, which in turn directly suppressed the transcription of major lipogenic genes FASN to reduce tumor growths. Furthermore, either PKM2 inhibitor-Shikonin or FASN inhibitor-TVB-3166 alone induced a strong antiproliferative and anticolony forming effect in bladder cancer cell line. The combination of both inhibitors exhibits a super synergistic effect on blocking the bladder cancer cells growth. It provides a new target and scientific basis for the treatment of bladder cancer.
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