糖酵解
PI3K/AKT/mTOR通路
厌氧糖酵解
肝细胞癌
癌症研究
蛋白激酶B
化学
内科学
医学
磷酸化
酶
信号转导
生物化学
作者
Xiaoling Zhang,Hao Líu,Haidong Wang,Rongjie Zhao,Qian Lu,Yunlong Liu,Yicheng Han,LuluRen,Hongming Pan,Weidong Han
标识
DOI:10.1007/s00018-022-04601-x
摘要
Hepatocellular carcinoma (HCC) is one of the most common malignancies with high morbidity and mortality. Beta-1,3-galactosyltransferase 5 (b3galt5) plays crucial roles in protein glycosylation, but its function in HCC remains unclear. Here, we investigated the role and underlying mechanism of b3galt5 in HCC. We found that b3galt5 is highly expressed and associated with a poor prognosis in HCC patients. In vitro studies showed that b3galt5 promoted the proliferation and survival of HCC cells. We also demonstrated that b3galt5 deficiency suppressed hepatocarcinogenesis in DEN/TCPOBOP-induced HCC. Further investigation confirmed that b3galt5 promoted aerobic glycolysis in HCC. Mechanistically, b3galt5 promoted glycolysis by activating the mTOR/p70s6k pathway through O-linked glycosylation modification on mTOR. Moreover, p70s6k inhibition reduced the expression of key glycolytic enzymes and the glycolysis rate in b3galt5-overexpressing cells. Our study uncovers a novel mechanism by which b3galt5 mediates glycolysis in HCC and highlights the b3galt5-mTOR/p70s6k axis as a potential target for HCC therapy.
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