期刊
CANCER RESEARCH
卷 78, 期 11, 页码 3041-3053出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-17-3776
关键词
-
类别
资金
- Ministry of Science and Technology of the People's Republic of China (China National Science and Technology Major Project) [2016YFA0101203]
- National Natural Science Foundation of China [81372555, 81402080]
- Chongqing Science and Technology Commission [cstc2015jcyjA10114]
Potassium ion channels are emerging as promalignant factors involved in cancer progression. In this study, we found that invading humangastric cancer cells express high levels of inwardly rectifying potassium channel 2.1 (Kir2.1). Silencing Kir2.1 markedly reduced the invasive and metastatic capabilities as well as the epithelial-mesenchymal transition (EMT) of gastric cancer cells. The promalignant nature of Kir2.1 in gastric cancer cells was independent of potassium permeation but relied on its interaction with serine/threonine-protein kinase 38 (Stk38) to inhibit ubiquitination and degradation of mitogen-activated protein kinase kinase kinase 2 (MEKK2). Degradation of MEKK2 was mediated by small mothers against decapentaplegic-specific E3 ubiquitin protein ligase 1 (Smurf1), which resulted in activation of the MEK1/2-ERK1/2-Snail pathway in gastric cancer cells. In human gastric cancer tissues, expression was high and positively correlated with invasion depth and metastatic status of the tumors as well as poor overall patient survival. Cox regression analysis identified Kir2.1 as an independent prognostic indicator for patients with gastric cancer. Our results suggest that Kir2.1 is an important regulator of gastric cancer malignancy and acts as a novel prognostic marker and a therapeutic target for gastric cancer. Significance: Kir2.1 contributes to invasion and metastasis by a noncanonical ion permeation-independent signaling pathway and may act as a novel prognostic marker and therapeutic target for gastric cancer. (C) 2018 AACR.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据