The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming

被引：65

作者：

Liem Phan ^{[1
,2
]}

Chou, Ping-Chieh ^{[1
,2
]}

Velazquez-Torres, Guermarie ^{[1
,2
]}

Samudio, Ismael ^{[3
]}

Parreno, Kenneth ^{[1
]}

Huang, Yaling ^{[1
,2
]}

Tseng, Chieh ^{[1
,2
]}

Thuy Vu ^{[1
,2
]}

Gully, Chris ^{[1
,2
]}

Su, Chun-Hui ^{[1
,2
]}

Wang, Edward ^{[1
,2
]}

Chen, Jian ^{[1
]}

Choi, Hyun-Ho ^{[1
,2
]}

Fuentes-Mattei, Enrique ^{[1
]}

Shin, Ji-Hyun ^{[1
,2
]}

Shiang, Christine ^{[2
,4
]}

Grabiner, Brian ^{[1
,2
]}

Blonska, Marzenna ^{[1
]}

Skerl, Stephen ^{[1
]}

Shao, Yiping ^{[5
]}

Cody, Dianna ^{[5
]}

Delacerda, Jorge ^{[5
]}

Kingsley, Charles ^{[5
]}

Webb, Douglas ^{[5
]}

Carlock, Colin ^{[1
,2
]}

Zhou, Zhongguo ^{[1
]}

Hsieh, Yun-Chih ^{[1
]}

Lee, Jaehyuk ^{[5
]}

Elliott, Andrew ^{[5
]}

Ramirez, Marc ^{[5
]}

Bankson, Jim ^{[5
]}

Hazle, John ^{[5
]}

Wang, Yongxing ^{[1
]}

Li, Lei ^{[6
]}

Weng, Shaofan ^{[6
]}

Rizk, Nibal ^{[1
]}

Wen, Yu Ye ^{[1
]}

Lin, Xin ^{[1
]}

Wang, Hua ^{[6
]}

Wang, Huamin ^{[6
]}

Zhang, Aijun ^{[7
]}

Xia, Xuefeng ^{[7
]}

Wu, Yun ^{[6
]}

Habra, Mouhammed ^{[8
]}

Yang, Wei ^{[4
]}

Pusztai, Lajos ^{[9
]}

Yeung, Sai-Ching ^{[8
,10
]}

Lee, Mong-Hong ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA

[2] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA

[3] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[7] Methodist Hosp Res Inst, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Endocrinol Neoplasia & Hormonal Disorders, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Emergency Med, Houston, TX 77030 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

美国国家卫生研究院;

关键词：

STRUCTURAL BASIS; MOTILITY FACTOR; TUMOR-GROWTH; MYC; BINDING; GLYCOLYSIS; P53; GLUTAMINOLYSIS; DETERMINANTS; LACTATE;

D O I：

10.1038/ncomms8530

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：

Extensive reprogramming of cellular energy metabolism is a hallmark of cancer. Despite its importance, the molecular mechanism controlling this tumour metabolic shift remains not fully understood. Here we show that 14-3-3 sigma regulates cancer metabolic reprogramming and protects cells from tumorigenic transformation. 14-3-3 sigma opposes tumour-promoting metabolic programmes by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3 sigma demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3 sigma expression levels predict overall and recurrence-free survival rates, tumour glucose uptake and metabolic gene expression in breast cancer patients. Thus, these results highlight that 14-3-3 sigma is an important regulator of tumour metabolism, and loss of 14-3-3 sigma expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3 sigma in tumours could be a promising direction for targeted anticancer metabolism therapy development in future.

引用

页数：16

共 50 条

[1] The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming
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Chris Gully
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