DUSP1 inhibits cell proliferation, metastasis and invasion and angiogenesis in gallbladder cancer

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// Jiliang Shen 1, * , Senjun Zhou 1, * , Liang Shi 1, * , Xiaolong Liu 1 , Hui Lin 1 , Hong Yu 1 , Xiaoliang 1 , Jiacheng Tang 1 , Tunan Yu 1 , Xiujun Cai 1 1 Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China * These authors contributed equally to this work Correspondence to: Xiujun Cai, email: cxjzu@hotmail.com Keywords: DUSP1, gallbladder cancer, metastasis, angiogenesis, MMP2 Received: September 05, 2015      Accepted: December 25, 2016      Published: January 25, 2017 ABSTRACT DUSP1/MKP1 is a dual-specific phosphatase that regulates MAPK activity and is known to play a key role in tumor biology. Its function in gallbladder cancer (GBC) remains largely unknown, however. By exploring its activities in two GBC cell lines (SGC996 and GBC-SD), DUSP1 was found to inhibit GBC cell proliferation, migration and invasion. Moreover, DUSP1 inhibited GBC growth and metastasis in nude mice subcutaneously xenografted with SGC996 cells. The tumor suppression appeared to be mediated via the DUSP1-pERK/MAPK-MMP2 signal pathway. Angiogenesis was associated with the tumor metastasis in the mouse model and was impaired by DUSP1, which suppressed VEGF expression. These results suggest that DUSP1 suppresses GBC growth and metastasis by targeting the DUSP1-pERK-MMP2/VEGF axis. Identification of the DUSP1-pERK-MMP2/VEGF signals may provide new biomarkers and/or therapeutic targets to better suppress GBC metastasis in the future.