The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming.
The cell cycle regulator 14-3-3σ opposes and reverses cancer metabolic reprogramming.
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DOI：
10.1038/ncomms8530
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发表时间：
2015-07-16
影响因子：
16.6
通讯作者：
Lee MH
中科院分区：
文献类型：
--
作者：
Phan L;Chou PC;Velazquez-Torres G;Samudio I;Parreno K;Huang Y;Tseng C;Vu T;Gully C;Su CH;Wang E;Chen J;Choi HH;Fuentes-Mattei E;Shin JH;Shiang C;Grabiner B;Blonska M;Skerl S;Shao Y;Cody D;Delacerda J;Kingsley C;Webb D;Carlock C;Zhou Z;Hsieh YC;Lee J;Elliott A;Ramirez M;Bankson J;Hazle J;Wang Y;Li L;Weng S;Rizk N;Wen YY;Lin X;Wang H;Wang H;Zhang A;Xia X;Wu Y;Habra M;Yang W;Pusztai L;Yeung SC;Lee MH
细胞能量代谢的广泛重编程是癌症的标志。尽管其重要性，控制这种肿瘤代谢转变的分子机制仍然没有完全理解。在这里，我们表明14-3-3σ调节癌症代谢重编程并保护细胞免受致瘤转化。14-3-3σ通过增强c-Myc多聚泛素化和随后的降解来对抗促肿瘤代谢程序。图14-3-3σ显示了对癌症糖酵解、胞氨分解、线粒体生物发生和肿瘤的其他主要代谢过程的抑制作用。重要的是，14-3-3σ表达水平预测乳腺癌患者的总体和无复发生存率、肿瘤葡萄糖摄取和代谢基因表达。因此，这些结果强调了14-3-3σ是肿瘤代谢的重要调节剂，并且14-3-3σ表达的丧失对于癌症代谢重编程是至关重要的。我们预期，提高14-3-3σ在肿瘤中的功能可能是未来靶向抗癌代谢治疗发展的一个有希望的方向。
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 14-3-3σ regulates cancer metabolic reprogramming and protects cells from tumourigenic transformation. 14-3-3σ opposes tumour-promoting metabolic programs by enhancing c-Myc poly-ubiquitination and subsequent degradation. 14-3-3σ demonstrates the suppressive impact on cancer glycolysis, glutaminolysis, mitochondrial biogenesis and other major metabolic processes of tumours. Importantly, 14-3-3σ 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 14-3-3σ is an important regulator of tumour metabolism, and loss of 14-3-3σ expression is critical for cancer metabolic reprogramming. We anticipate that pharmacologically elevating the function of 14-3-3σ in tumours could be a promising direction for targeted anti-cancer metabolism therapy development in future.