ME1 promotes basal-like breast cancer progression and associates with poor prognosis

被引:44
作者
Liao, Ruocen [1 ,2 ,3 ]
Ren, Guoping [4 ]
Liu, Huixin [1 ,2 ,3 ]
Chen, Xingyu [1 ,2 ,3 ]
Cao, Qianhua [1 ,2 ,3 ]
Wu, Xuebiao [1 ,2 ,3 ]
Li, Jun [1 ,2 ,3 ]
Dong, Chenfang [1 ,2 ,3 ]
机构
[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Pathol & Pathophysiol, Hangzhou 310058, Zhejiang, Peoples R China
[2] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Surg Oncol,Breast Ctr, Hangzhou 310058, Zhejiang, Peoples R China
[3] Zhejiang Univ, Zhejiang Key Lab Dis Prote, Sch Med, Hangzhou 310058, Zhejiang, Peoples R China
[4] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Dept Pathol, Hangzhou 310058, Zhejiang, Peoples R China
基金
国家重点研发计划;
关键词
METABOLISM; REPRESSION; SNAIL; P53;
D O I
10.1038/s41598-018-35106-y
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Basal-like breast cancer (BLBC) is associated with a poor clinical outcome due to the few treatment options and absence of effective targeted agents. Here, we show that malic enzyme 1 (ME1) is dramatically upregulated in BLBC due to ME1 copy number amplification. ME1 expression increases glucose uptake and lactate production, and reduces oxygen consumption, leading to aerobic glycolysis. ME1 expression promotes, whereas knockdown of ME1 expression suppresses tumorigenicity. In breast cancer patients, ME1 expression is positively correlated with large tumor size, high grade, poor survival, and chemotherapy resistance. Our study not only contributes to a new understanding of how metabolic reprogramming contributes to BLBC progression, but also provides a potential prognostic marker and therapeutic target for this challenging disease.
引用
收藏
页数:10
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