Department of General Surgery, Cangnan County People's Hospital, Wenzhou, Zhejiang 325800, P.R. China.
Mol Med Rep. 2018 Jun;17(6):7645-7651. doi: 10.3892/mmr.2018.8806. Epub 2018 Mar 28.
Aberrant activation of β‑catenin/transcription factor 7 like 2 (TCF7L2) signaling is frequently observed during the progression of hepatocellular carcinoma (HCC). However, regulation of the nuclear β‑catenin/TCF7L2 complex remains largely unknown. In the present study, immunoprecipitation and glutathione S‑transferase pull‑down assays identified transcription termination factor‑1 interacting protein 5 (TIP5) as a binding partner of TCF7L2. TIP5 activated β‑catenin/TCF7L2 signaling by enhancing the interaction between β‑catenin and TCF7L2. The results from quantitative polymerase chain reaction and western blot analysis indicated that TIP5 was upregulated in clinical HCC samples. In addition, TIP5 positively regulated the proliferation of HCC cells in the MTT assay, colony formation in the soft agar assay, migration in the Boyden chamber assay and epithelial‑mesenchymal transition of HCC cells by activating β‑catenin/TCF7L2 signaling. Therefore, the results of the present study demonstrate that TIP5 serves an oncogenic role in HCC by activating β‑catenin/TCF7L2 signaling, suggesting that TIP5 may be a promising therapeutic target for HCC.
β-连环蛋白/转录因子 7 样 2（TCF7L2）信号的异常激活在肝细胞癌（HCC）的进展过程中经常观察到。然而，核β-连环蛋白/TCF7L2 复合物的调节在很大程度上仍然未知。在本研究中，免疫沉淀和谷胱甘肽 S-转移酶 pull-down 测定鉴定转录终止因子-1 相互作用蛋白 5（TIP5）为 TCF7L2 的结合伴侣。TIP5 通过增强β-连环蛋白和 TCF7L2 之间的相互作用来激活β-连环蛋白/TCF7L2 信号。定量聚合酶链反应和 Western blot 分析的结果表明，TIP5 在临床 HCC 样本中上调。此外，TIP5 通过激活β-连环蛋白/TCF7L2 信号正向调节 MTT 测定中 HCC 细胞的增殖、软琼脂测定中的集落形成、Boyden 室测定中的迁移和 HCC 细胞的上皮-间充质转化。因此，本研究的结果表明，TIP5 通过激活β-连环蛋白/TCF7L2 信号在 HCC 中发挥致癌作用，提示 TIP5 可能是 HCC 的有前途的治疗靶点。
