TNFAIP8 interacts with LATS1 and promotes aggressiveness through regulation of Hippo pathway in hepatocellular carcinoma

// Qianze Dong 1 , Lin Fu 1 , Yue Zhao 1 , Chengyao Xie 1 , Qingchang Li 1 , Enhua Wang 1 1 College of Basic Medical Sciences and Department of Pathology, First Affiliated Hospital, China Medical University Shenyang, Liaoning, China Correspondence to: Enhua Wang, email: wangenhuacmu@hotmail.com Keywords: TNFAIP8, hepatocellular carcinoma, YAP, Hippo Received: November 02, 2016      Accepted: December 28, 2016      Published: February 01, 2017 ABSTRACT Although TNFAIP8 overexpression has been implicated in several human cancers, its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. Our study demonstrated that TNFAIP8 overexpression in primary HCC samples correlated with TNM stage, recurrence, poor prognosis and served as an independent favorable prognostic factor. We further showed that TNFAIP8 upregulated cell proliferation, migration, invasion and xenograft tumor growth of HCC cells. In addition, TNFAIP8 overexpression inhibited YAP phosphorylation, increased its nuclear localization and stabilization, leading to upregulation of cyclin proteins, CTGF and cell proliferation. We also found that TNFAIP8 could interact with LATS1 and decreased its phosphorylation. Depletion of LATS1 and YAP by siRNA blocked the biological effects of TNFAIP8. Collectively, the present study provides a novel finding that TNFAIP8 promotes HCC progression through LATS1-YAP signaling pathway. TNFAIP8 may serve as a candidate biomarker for poor prognosis and a target for new therapies.