BAG3 directly stabilizes Hexokinase 2 mRNA and promotes aerobic glycolysis in pancreatic cancer cells

被引：70

作者：

An, Ming-Xin ^{[1
,2
,3
]}

Li, Si ^{[1
]}

Yao, Han-Bing ^{[1
]}

Li, Chao ^{[1
]}

Wang, Jia-Mei ^{[1
]}

Sun, Jia ^{[1
]}

Li, Xin-Yu ^{[1
]}

Meng, Xiao-Na ^{[1
]}

Wang, Hua-Qin ^{[1
,2
,3
]}

机构：

[1] China Med Univ, Dept Biochem & Mol Biol, Shenyang, Liaoning, Peoples R China

[2] China Med Univ, Key Lab Cell Biol, Minist Publ Hlth, Shenyang, Liaoning, Peoples R China

[3] China Med Univ, Key Lab Med Cell Biol, Minist Educ, Shenyang, Liaoning, Peoples R China

来源：

JOURNAL OF CELL BIOLOGY | 2017年 / 216卷 / 12期

基金：

中国国家自然科学基金;

关键词：

ANTIAPOPTOTIC PROTEIN BAG3; APOPTOSIS; DECAY; PATHWAY;

D O I：

10.1083/jcb.201701064

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level. BAG3 interacted with HK2 mRNA, and the degree of BAG3 expression altered recruitment of the RNA-binding proteins Roquin and IMP3 to the HK2 mRNA. BAG3 knockdown destabilized HK2 mRNA via promotion of Roquin recruitment, whereas BAG3 overexpression stabilized HK2 mRNA via promotion of IMP3 recruitment. Collectively, our results show that BAG3 promotes reprogramming of glucose metabolism via interaction with HK2 mRNA in PDAC cells, suggesting that BAG3 may be a potential target in the aerobic glycolysis pathway for developing novel anticancer agents.

引用

页码：4091 / 4105

页数：15

共 39 条

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Hexokinase 2 promotes tumor growth and metastasis by regulating lactate production in pancreatic cancer [J].