SCI 17 January 2022

STAT proteins in cancer: orchestration of metabolism

Li YJ, Zhang C, Martincuks A, Herrmann A, Yu H. STAT proteins in cancer: orchestration of metabolism. Nat Rev Cancer. 2023 Jan 3. doi: 10.1038/s41568-022-00537-3. Epub ahead of print. PMID: 36596870.

Corresponding author：Hua Yu, Department of Immuno-Oncology, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA. e-mail: hyu@coh.org

Abstract摘要  

Reprogrammed metabolism is a hallmark of cancer. However, the metabolic dependency of cancer, from tumour initiation through disease progression and therapy resistance, requires a spectrum of distinct reprogrammed cellular metabolic pathways. These pathways include aerobic glycolysis, oxidative phosphorylation, reactive oxygen species generation, de novo lipid synthesis, fatty acid β-oxidation, amino acid (notably glutamine) metabolism and mitochondrial metabolism. This Review highlights the central roles of signal transducer and activator of transcription (STAT) proteins, notably STAT3, STAT5, STAT6 and STAT1, in orchestrating the highly dynamic metabolism not only of cancer cells but also of immune cells and adipocytes in the tumour microenvironment. STAT proteins are able to shape distinct metabolic processes that regulate tumour progression and therapy resistance by transducing signals from metabolites, cytokines, growth factors and their receptors; defining genetic programmes that regulate a wide range of molecules involved in orchestration of metabolism in cancer and immune cells; and regulating mitochondrial activity at multiple levels, including energy metabolism and lipid-mediated mitochondrial integrity. Given the central role of STAT proteins in regulation of metabolic states, they are potential therapeutic targets for altering metabolic reprogramming in cancer.

代谢重编程是癌症的一个特征。然而，癌症的代谢依赖性，从肿瘤起始到疾病进展和治疗耐药性，需要一系列不同的重编程细胞代谢途径。这些途径包括有氧糖酵解、氧化磷酸化、活性氧生成、脂质从头合成、脂肪酸β氧化、氨基酸（尤其是谷氨酰胺）代谢和线粒体代谢。这篇综述强调了信号传导及转录激活蛋白（STAT）蛋白，特别是STAT3、STAT5、STAT6和STAT1，在肿瘤微环境中调控癌细胞以及免疫细胞和脂肪细胞高度动态代谢的核心作用。STAT蛋白能够形成不同的代谢过程，通过传导来自代谢分子、细胞因子、生长因子及其受体的信号来调节肿瘤进展和治疗耐药性；确定调控癌症和免疫细胞代谢中涉及的广泛分子的遗传程序；并在多个水平上调节线粒体活性，包括能量代谢和脂质介导的线粒体完整。鉴于STAT蛋白在代谢状态调节中的核心作用，它们是改变癌症代谢重编程的潜在治疗靶点。

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