机构：[1]Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China[2]University of Chinese Academy of Sciences, Beijing, 100049, China[3]Obstetrics and Gynecology Medical Center of Severe Cardiovascular Disease of Beijing, Anzhen Hospital, Capital Medical University, Beijing, 100029, China临床科室妇产科首都医科大学附属安贞医院
Cadherin switch is an initiating factor of epithelial-mesenchymal transition (EMT) and is intimately correlated with cancer metastatic potential; however, its underlying mechanisms remain unclear. Here, using a transforming growth factor-g (TGF-beta)-induced EMT model, we provide explicit evidence that CD146, with elevated expression and activity in a variety of cancers, is a key factor involved in the cadherin switch. We show that CD146 can be induced by TGF-beta signaling. Moreover, CD146 expression is positively correlated with the activation levels of STAT3/Twist and ERK pathways. Transcriptional response of the CD146/STAT3/Twist cascade inhibits E-cadherin expression, whereas the CD146/ERK cascade enhances N-cadherin expression. CD146 overexpression also significantly promotes EMT in both mouse embryonic fibroblasts (MEFs) and ovarian cancer cells. Clinically, ovarian cancer patients with detectable CD146 expression had a significantly lower survival rate than that of patients without CD146 expression. Furthermore, CD146-deficient MEFs exhibited decreased motility as a result of reversion in this cadherin switch, strongly suggesting that targeting CD146 is a potential strategy for cancer treatment. Therefore, CD146-mediated regulation of the E-cadherin-to-N-cadherin switch provides an insight into the general mechanisms of EMT as well as cancer metastasis.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [91529306]; Strategic Priority Program of the Chinese Academy of Sciences [XDA12020207]; National Basic Research Program of ChinaNational Basic Research Program of China [2015CB553705]
第一作者机构：[1]Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China[2]University of Chinese Academy of Sciences, Beijing, 100049, China
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China[2]University of Chinese Academy of Sciences, Beijing, 100049, China[3]Obstetrics and Gynecology Medical Center of Severe Cardiovascular Disease of Beijing, Anzhen Hospital, Capital Medical University, Beijing, 100029, China[*1]Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China
推荐引用方式(GB/T 7714)：
Ma Yanbin,Zhang Haofeng,Xiong Chaoliang,et al.CD146 mediates an E-cadherin-to-N-cadherin switch during TGF-beta signaling-induced epithelial-mesenchymal transition[J].CANCER LETTERS.2018,430:201-214.doi:10.1016/j.canlet.2018.05.016.
APA：
Ma, Yanbin,Zhang, Haofeng,Xiong, Chaoliang,Liu, Zheng,Xu, Qingji...&Yan, Xiyun.(2018).CD146 mediates an E-cadherin-to-N-cadherin switch during TGF-beta signaling-induced epithelial-mesenchymal transition.CANCER LETTERS,430,
MLA：
Ma, Yanbin,et al."CD146 mediates an E-cadherin-to-N-cadherin switch during TGF-beta signaling-induced epithelial-mesenchymal transition".CANCER LETTERS 430.(2018):201-214
医学