标题:Bone morphogenetic protein 2 mediates epithelial-mesenchymal transition via AKT and ERK signaling pathways in gastric cancer
作者:Liao, Anyan;Wang, Weijie;Sun, Dawei;Jiang, Yuliang;Tian, Suqing;Li, Jinna;Yang, Xiangshan;Shi, Ranran
作者机构:[Liao, A] Department of Radiation Oncology, Peking University 3rd Hospital, Beijing,, 100191, China, Department of Emergency Surgery, Qilu Hospital of 更多
通讯作者:Liao, AY
通讯作者地址:[Liao, AY]Peking Univ, Dept Radiat Oncol, Hosp 3, Beijing 100191, Peoples R China.
来源:Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine
出版年:2015
卷:36
期:4
页码:2773-2778
DOI:10.1007/s13277-014-2901-1
关键词:BMP2;EMT;AKT;ERK;Gastric cancer
摘要:Although deregulation of bone morphogenetic protein 2 (BMP2) signaling has been linked to various types of cancers, the relationships between abnormal activation of these signaling pathways and tumorigenesis are not clear in gastric cancer. We hypothesized that BMP2 might be involved in epithelial-mesenchymal transition (EMT) process of gastric cancer. Here, BMPR-II activation and inhibition in gastric cancer cell line AGS were induced with exogenous BMP2 and with BMPR-II small interfering RNA (siRNA), respectively. BMPR-II downstream signal molecules AKT, ERK phosphorylation, and EMT biomarkers (vimentin, snail, N-cadherin, and E-cadherin) were tested using the Western blot. In the present study, our results showed that BMP2 can induce AKT and ERK phosphorylation in a dose-dependent method, and endogenous BMPR-II can be inhibited completely by BMPR-II siRNA in AGS. Notably BMP2 alone treatment can induce the up-regulation of vimentin, snail, and N-cadherin in AGS cells, besides, the down-regulation of E-cadherin also occurred. On the contrary, BMPR-II siRNA significantly prohibited BMP2-induced AKT and ERK phosphorylation, at the same time, EMT biomarkers changes were not observed. On the other hand, BMPR-II knockdown could significantly affect AGS wound closure and the migration ability (p<0.001) compared to control siRNA and BMP2 alone. In conclusion, this study suggested that EMT process can be triggered by the BMP2/BMPR axis in gastric cancer and then involved in the tumor cell migration, invasion, and metastasis via the activation of PI3K/AKT and MEK/ERK pathways. Our study lays a new foundation for the treatment of gastric cancer through antagonizing BMP2 system.
收录类别:SCOPUS;SCIE
WOS核心被引频次:19
Scopus被引频次:17
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84936743335&doi=10.1007%2fs13277-014-2901-1&partnerID=40&md5=fd23328788754cfee79b0fbccd0076a0
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