WIP1 stimulates migration and invasion of salivary adenoid cystic carcinoma by inducing MMP-9 and VEGF-C

// Ya-ling Tang 1, 2 , Xin Liu 2 , Shi-yu Gao 2 , Hao Feng 2 , Ya-ping Jiang 2 , Sha-sha Wang 2 , Jing Yang 2 , Jian Jiang 2 , Xiang-rui Ma 2 , Ya-jie Tang 3 , Yu Chen 1 , Xin-hua Liang 2, 4 1 Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People’s Republic of China 2 State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People’s Republic of China 3 Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, People’s Republic of China 4 Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan 610041, People’s Republic of China Correspondence to: Xin-hua Liang, e-mail: lxh88866@scu.edu.cn , drliangxinhua@aliyun.com Keywords: wild-type p53 induced phosphatase 1 (WIP1), adenoid cystic carcinoma (ACC), salivary gland, invasion, metastasis Received: January 09, 2015      Accepted: February 23, 2015      Published: March 06, 2015 ABSTRACT The wild-type p53 induced phosphatase 1 (WIP1) is an oncogene overexpressed in a variety of human cancers. Here, we demonstrated that WIP1 silencing reduced MMP-9 and VEGF-C expression as well as migration and invasion of salivary adenoid cystic carcinoma (ACC) cells. Overexpression of MMP-9 or VEGF-C restored migration and invasion in WIP1 knockdown cells, indicating that MMP-9 and VEGF-C are downstream targets of WIP1 signaling. Levels of cyclin D1 and c-Myc, targets of Wnt/β-catenin pathway, were significantly decreased by WIP1 silencing. In addition, WIP1 expression was positively associated with metastasis and prognosis of ACC patients as well as with MMP-9 or VEGF-C in ACC tissues.