胃Lgr5^(+)干细胞、Mist1^(+)干细胞和Cck2r^(+)干细胞癌变的分子机制  

Molecular mechanisms of gastric Lgr5^(+)stem cells,Mist1^(+)stem cells and Cck2r^(+)stem cells in carcinogenesis

作　　者：刘先勇 Liu Xianyong(Department of Integrated Traditional Chinese and Western Medicine,Jiangning Hospital,Nanjing Medical University,Nanjing 211100,China)

机构地区：[1]南京医科大学附属江宁医院中西医结合科,211100

出　　处：《中华细胞与干细胞杂志（电子版）》2023年第3期183-188,共6页Chinese Journal of Cell and Stem Cell（Electronic Edition）

基　　金：南京市卫生科技发展专项资金项目计划(YKK22225)。

摘　　要：胃干细胞(GSCs)在肠型胃癌(IGC)发生中发挥重要作用。GSCs主要包括富含亮氨酸重复序列的G蛋白偶联受体-5^(+)干细胞(Lgr5^(+)SCs),肌肉、小肠和胃表达因子1(Mist1)^(+)SCs和胃窦胆囊收缩素2型受体(Cck2r)^(+)SCs等。本文综述这三种GSCs癌变的分子机制,发现经典的Wnt信号通路(cWnt)-Notch动态平衡失调驱动IGC的发生。cWnt-磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)或cWnt-Ras信号通路被激活和Notch信号通路被抑制是这几个胃干细胞癌变的普遍特点;激活Notch/胶质瘤相关癌基因同源物(Gli)2/哺乳动物雷帕霉素靶蛋白(mTOR)下调cWnt是癌变的另外一种机制,深入研究这两种癌变分子机制或能为IGC治疗提供新思路。Gastric stem cells(GSCs)play an important role in developing the intestinal gastric cancer(IGC).GSCs mainly include leucine-rich repeat-containing G-protein coupled receptor 5^(+)stem cells(Lgr5^(+)SCs),muscle,intestine and stomach expression 1(Mist1)^(+)SCs,and antral cholecystokinin type 2 receptor(Cck2r)^(+)stem cells,etc.This article reviews the molecular mechanisms of carcinogenesis of the three types of gastric stem cells.It is found that the canonical wnt signal pathway(cWnt)-Notch dynamic imbalance drives the occurrence of intestinal-type gastric cancer(IGC).The activation of the cWnt-phosphatidylinositol 3-kinase and protein kinase B(PI3K/Akt)or cWnt-Ras signaling pathway and the inhibition of the Notch signaling pathway are common characteristics of gastric stem cell carcinogenesis in these cells;Activating Notch/Glioma-associated oncogene homolog(Gli)2/mammalian target of rapamycin(mTOR)and downregulating cWnt is another mechanism of carcinogenesis.Furthermore,more researche on these two molecular mechanisms of carcinogenesis may provide new ideas for IGC treatment.

关 键 词：WNT信号通路 NOTCH信号通路 胃 干细胞 肠型胃癌 

分 类 号：R73[医药卫生—肿瘤]