文章：

STAT蛋白在癌症中的作用：代谢的编排

STAT proteins in cancer: orchestration of metabolism

原文发布日期：2023-01-03

DOI: 10.1038/s41568-022-00537-3

类型: Review Article

开放获取: 否

英文摘要：

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.

摘要翻译： 

代谢重编程是癌症的一个标志。然而，从肿瘤发生到疾病进展及治疗抵抗，癌细胞的代谢依赖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、新生脂质合成、脂肪酸β-氧化、氨基酸（特别是谷氨酰胺）代谢及线粒体代谢。本综述重点探讨信号转导与转录激活因子（STAT）蛋白——特别是STAT3、STAT5、STAT6和STAT1——在协调肿瘤微环境中癌细胞、免疫细胞及脂肪细胞高度动态代谢中的核心作用。STAT蛋白通过以下机制塑造调控肿瘤进展和治疗抵抗的特定代谢过程：转导代谢物、细胞因子、生长因子及其受体信号；定义调节癌症和免疫细胞代谢协调中广泛分子的遗传程序；在多个层面调控线粒体活动，包括能量代谢和脂质介导的线粒体完整性。鉴于STAT蛋白在代谢状态调控中的核心作用，它们有望成为改变癌症代谢重编程的潜在治疗靶点。

原文链接：

STAT proteins in cancer: orchestration of metabolism