Silencing PPA1 inhibits human epithelial ovarian cancer metastasis by suppressing the Wnt/β-catenin signaling pathway

// Haiying Niu 1, * , Wei Zhou 2, * , Yingxi Xu 3 , Zhiqi Yin 4 , Wenzhi Shen 2 , Zhen Ye 2 , Yanhua Liu 2 , Yanan Chen 2 , Shuang Yang 2 , Rong Xiang 2 , Lina Wang 3 and Pengpeng Qu 5 1 Department of Gynecology and Obstetrics, Tianjin First Center Hospital, Tianjin, China 2 Department of Immunology, Nankai University School of Medicine, Tianjin, China 3 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences, Tianjin, China 4 Department of Pathology, Tianjin First Center Hospital, Tianjin, China 5 Department of Gynecology Oncology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin, China * These authors have contributed equally to this work Correspondence to: Lina Wang, email: wanglina@ihcams.ac.cn Pengpeng Qu, email: qu.pengpeng@hotmail.com Keywords: PPA1, epithelial ovarian cancer, metastasis, Wnt/β-catenin Received: January 18, 2017     Accepted: June 19, 2017     Published: July 18, 2017 ABSTRACT Inorganic pyrophosphatase (PPA1) activity is a key determinant of cellular inorganic pyrophosphate levels, and its expression is correlated with growth of several solid tumors. To investigate this relationship, we first examined PPA1 expression in human epithelial ovarian cancer (EOC) samples, and found that PPA1 was overexpressed in tumors from EOC patients. Higher PPA1 levels correlated with advanced grades, stages, and poor survival in EOC patients. Examination of PPA1 function in EOC revealed that silencing PPA1 inhibited EOC migration, epithelial-mesenchymal transition (EMT), and metastasis in vitro and in vivo . In addition, PPA1 may promote the dephosphorylation and translocation of β-catenin. These results demonstrate that silencing PPA1 inhibits EOC metastasis by suppressing the Wnt/β-catenin signaling pathway. Strategies for downregulating PPA1 may have therapeutic potential for the prevention and treatment of EOC.