TNFAIP8 interacts with LATS1 and promotes aggressiveness through regulation of Hippo pathway in hepatocellular carcinoma.
TNFAIP8 interacts with LATS1 and promotes aggressiveness through regulation of Hippo pathway in hepatocellular carcinoma.
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TNFAIP8 与 LATS1 相互作用并通过调节肝细胞癌中的 Hippo 通路促进侵袭性
DOI：
10.18632/oncotarget.14938
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发表时间：
2017-02-28
期刊：
影响因子：
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通讯作者：
Wang E
中科院分区：
文献类型：
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作者：
Dong Q;Fu L;Zhao Y;Xie C;Li Q;Wang E
尽管TNFAIP 8过表达与几种人类癌症有关，但其在肝细胞癌（HCC）中的临床意义和生物学功能仍然未知。我们的研究表明，原发性肝癌组织中TNFAIP 8过表达与TNM分期、复发、预后不良相关，是一个独立的有利预后因素。我们进一步表明TNFAIP 8上调肝癌细胞的细胞增殖、迁移、侵袭和异种移植肿瘤生长。此外，TNFAIP 8过表达抑制雅普磷酸化，增加其核定位和稳定性，导致细胞周期蛋白、CTGF和细胞增殖的上调。我们还发现TNFAIP 8可以与LATS 1相互作用，并降低其磷酸化。通过siRNA去除LATS 1和雅普阻断了TNFAIP 8的生物学效应。总之，本研究提供了TNFAIP 8通过LATS 1-雅普信号通路促进HCC进展的新发现。TNFAIP 8可以作为预后不良的候选生物标志物和新疗法的靶点。
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.