TNFAIP8 interacts with LATS1 and promotes aggressiveness through regulation of Hippo pathway in hepatocellular carcinoma.
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.
College of Basic Medical Sciences and Department of Pathology, First Affiliated Hospital, China Medical University Shenyang, Liaoning, China.
Qianze
Q
Dong
College of Basic Medical Sciences and Department of Pathology, First Affiliated Hospital, China Medical University Shenyang, Liaoning, China.
Lin
L
Fu
College of Basic Medical Sciences and Department of Pathology, First Affiliated Hospital, China Medical University Shenyang, Liaoning, China.
Yue
Y
Zhao
College of Basic Medical Sciences and Department of Pathology, First Affiliated Hospital, China Medical University Shenyang, Liaoning, China.
Chengyao
C
Xie
College of Basic Medical Sciences and Department of Pathology, First Affiliated Hospital, China Medical University Shenyang, Liaoning, China.
Qingchang
Q
Li
College of Basic Medical Sciences and Department of Pathology, First Affiliated Hospital, China Medical University Shenyang, Liaoning, China.
Enhua
E
Wang
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D000090683:Hippo Signaling Pathway; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000090742:Serine-Threonine Kinase 3; D015398:Signal Transduction; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D000099317:Hippo Kinases
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D000090742:Serine-Threonine Kinase 3; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C404190:TNFAIP8 protein, human; C088374:YAP1 protein, human; C092745:LATS1 protein, human; C095566:STK4 protein, human; D000099317:Hippo Kinases; C097835:STK3 protein, human
Hippo; TNFAIP8; YAP; hepatocellular carcinoma