NID1, a new regulator of EMT required for metastasis and chemoresistance of ovarian cancer cells
Open Access
- 13 March 2017
- journal article
- research article
- Published by Impact Journals, LLC in Oncotarget
- Vol. 8 (20), 33110-33121
- https://doi.org/10.18632/oncotarget.16145
Abstract
// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Ya Zhou1, 2, *, Yuanyuan Zhu1, 2, *, Xiaoyan Fan1, 2, *, Chundong Zhang1, 2, Yitao Wang1, 2, Lian Zhang1, 2, Huan Zhang3, Tao Wen4, Kaina Zhang3, Xiao Huo5, Xue Jiang1, 2, Youquan Bu1, 2 and Ying Zhang1, 2 1Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China 2Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China 3College of Pharmacy, Chongqing Medical University, Chongqing 400016, China 4First Clinical College, Chongqing Medical University, Chongqing 400016, China 5College of Biomedical Engineering, Chongqing Medical University, Chongqing 400016, China *These authors contributed equally to this work Correspondence to: Ying Zhang, email: zhangying078@aliyun.com Keywords: ovarian cancer, NID1, EMT, metastasis, chemoresistance Abbreviations: ECM: extracellular matrix; EMT: epithelial-mesenchymal transition; FAK: focal adhesion kinase; MET: mesenchymal-epithelial transition; NID1: nidogen-1 Received: January 09, 2017 Accepted: February 08, 2017 Published: March 13, 2017 ABSTRACT Nidogen-1 (NID1) has been identified as a novel candidate diagnostic biomarker of ovarian cancer in our previous study. Nevertheless, the role of NID1 in the pathogenesis of ovarian cancer is unclear. In the present study, we demonstrated that NID1 was a mesenchymal associated gene and its high expression was significantly correlated with shorter overall survival of ovarian cancer patients. The ectopic expression of NID1 in OVCAR-3 cells revealed a epithelial-mesenchymal transition (EMT) phenotype accompanied by enhancement of motility, invasiveness and cisplatin resistance, whereas the knockdown of NID1 was sufficient to convert HEY cells into epithelial phenotype with decreased capability of motility, invasiveness and cisplatin resistance. Mechanistic studies disclosed that NID1 activated ERK/MAPK signaling pathway to promote EMT. Collectively, our findings have uncovered the molecular mechanisms of NID1 in promoting ovarian cancer metastasis and chemoresistance, and provide a rationale for the therapeutic potential of NID1 suppression in ovarian cancer.Keywords
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