NID1, a new regulator of EMT required for metastasis and chemoresistance of ovarian cancer cells

Abstract

// Ya Zhou 1, 2, * , Yuanyuan Zhu 1, 2, * , Xiaoyan Fan 1, 2, * , Chundong Zhang 1, 2 , Yitao Wang 1, 2 , Lian Zhang 1, 2 , Huan Zhang 3 , Tao Wen 4 , Kaina Zhang 3 , Xiao Huo 5 , Xue Jiang 1, 2 , Youquan Bu 1, 2 and Ying Zhang 1, 2 1 Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016, China 2 Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China 3 College of Pharmacy, Chongqing Medical University, Chongqing 400016, China 4 First Clinical College, Chongqing Medical University, Chongqing 400016, China 5 College 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.