Han Jie, Theiss Arianne L
Department of Internal Medicine, Division of Gastroenterology, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Inflamm Bowel Dis. 2014 Dec;20(12):2405-11. doi: 10.1097/MIB.0000000000000180.
Chronic inflammation predisposes tissue to cancer development. Individuals afflicted with inflammatory bowel diseases are at an increased risk of developing colorectal cancer depending on disease severity, duration, and management. The intestinal epithelium exhibits mitochondrial dysfunction during colitis and colitis-associated cancer. Signal Transducer and Activator of Transcription (Stat)-3 is a transcription factor involved in growth-promoting and antiapoptotic signaling pathways. In addition to its activities as a transcription factor, Stat3 resides in the mitochondria of cells where it is required for optimal electron transport chain activity and protects against stress-induced mitochondrial dysfunction. The function of mitochondrial Stat3 is not completely understood; dichotomous roles include protecting against cellular injury but also supporting malignant transformation. This review discusses the roles of Stat3 in the regulation of intestinal epithelial cell fate during colitis and colorectal cancer with an emphasis on mitochondrial dysfunction and the potential involvement of mitochondrial Stat3 during disease progression.
慢性炎症使组织易于发生癌症。患有炎症性肠病的个体根据疾病的严重程度、持续时间和治疗情况，患结直肠癌的风险会增加。在结肠炎和结肠炎相关癌症期间，肠上皮会出现线粒体功能障碍。信号转导和转录激活因子（Stat）-3是一种参与生长促进和抗凋亡信号通路的转录因子。除了作为转录因子的活性外，Stat3存在于细胞的线粒体中，在那里它是最佳电子传递链活性所必需的，并能防止应激诱导的线粒体功能障碍。线粒体Stat3的功能尚未完全了解；其双重作用包括防止细胞损伤，但也支持恶性转化。本综述讨论了Stat3在结肠炎和结直肠癌期间调节肠上皮细胞命运中的作用，重点是线粒体功能障碍以及线粒体Stat3在疾病进展过程中的潜在作用。
