文章：

STAT2调控结直肠肿瘤发生及抗癌药物耐药性

STAT2 Controls Colorectal Tumorigenesis and Resistance to Anti-Cancer Drugs

原文发布日期：15 November 2023

DOI: 10.3390/cancers15225423

类型: Article

开放获取: 是

英文摘要：

Colorectal cancer (CRC) is a significant socioeconomic burden in modern society and is accountable for millions of premature deaths each year. The role of signal transducer and activator of transcription 2 (STAT2)-dependent signaling in this context is not yet fully understood, and no therapies targeting this pathway are currently being pursued. We investigated the role of STAT2 in CRC using experimental mouse models coupled with RNA-sequencing (RNA-Seq) data and functional assays with anti-cancer agents in three-dimensional tumoroids.Stat2−/−mice showed greater resistance to the development of CRC in both inflammation-driven and inflammation-independent experimental CRC models. In ex vivo studies, tumoroids derived fromStat2−/−mice with the multiple intestinal neoplasia (Min) mutant allele of the adenomatous polyposis coli(Apc)locus exhibited delayed growth, were overall smaller and more differentiated as compared with tumoroids fromApcMin/+wildtype (WT) mice. Notably, tumoroids fromApcMin/+Stat2−/−mice were more susceptible to anti-cancer agents inducing cell death by different mechanisms. Our findings clearly indicated that STAT2 promotes CRC and suggested that interventions targeting STAT2-dependent signals might become an attractive therapeutic option for patients with CRC.

摘要翻译： 

结直肠癌（CRC）是现代社会的重大社会经济负担，每年导致数百万例过早死亡。信号转导与转录激活因子2（STAT2）依赖性信号通路在此背景下的作用尚未完全阐明，目前尚无针对该通路的疗法正在研发中。我们通过实验小鼠模型结合RNA测序数据，并在三维肿瘤类器官中采用抗癌药物进行功能实验，研究了STAT2在CRC中的作用。 在炎症驱动型和非炎症依赖型实验性CRC模型中，Stat2−/−小鼠均表现出更强的CRC发展抗性。离体实验显示，与ApcMin/+野生型（WT）小鼠相比，源自携带腺瘤性结肠息肉病（Apc）基因座多发性肠腺瘤（Min）突变等位基因的Stat2−/−小鼠的肿瘤类器官生长延迟、整体尺寸更小且分化程度更高。值得注意的是，ApcMin/+Stat2−/−小鼠的肿瘤类器官对不同作用机制的细胞死亡诱导型抗癌药物表现出更高的敏感性。我们的研究结果明确表明STAT2促进CRC发展，并提示针对STAT2依赖性信号的干预措施可能成为CRC患者具有潜力的治疗选择。

原文链接：

STAT2 Controls Colorectal Tumorigenesis and Resistance to Anti-Cancer Drugs