Farnesoid X receptor associates with β-catenin and inhibits its activity in hepatocellular carcinoma.
Farnesoid X receptor associates with β-catenin and inhibits its activity in hepatocellular carcinoma.
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DOI：
10.18632/oncotarget.2899
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发表时间：
2015-02-28
期刊：
影响因子：
--
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Liu X;Zhang X;Ji L;Gu J;Zhou M;Chen S
Wnt/β-catenin通路的暂时激活与法尼醇X受体（FXR）基因敲除小鼠自发性肝细胞癌（HCC）发生之间的关系尚不清楚。我们发现通过RNAi去除FXR的Huh 7细胞在体外显示出增强的细胞生长、迁移和侵袭，并加速裸鼠中的肿瘤异种移植物形成。这些表型通过RNAi同时敲低β-catenin而减弱。进一步证实FXR可以通过AF 1结构域与β-Catenin结合，破坏β-Catenin/TCF 4复合物的组装。FXR的激活减弱了β-Catenin/TCF 4的DNA结合活性，随后减弱了其靶基因cyclin D1的表达。重要的是，FXR表达在人HCC中显著降低，这一事件与β-连环蛋白的异常激活相关。这些数据表明FXR通过直接抑制Wnt/β-catenin途径作为HCC发展的负调节因子。
The association between the temporal activation of Wnt/β-catenin pathway and the spontaneous hepatocellular carcinoma (HCC) development in Farnesoid X receptor (FXR) knockout mice is not well understood. We found that Huh7 cells depleted with FXR by RNAi showed enhanced cell growth, migration and invasion in vitro and accelerated tumor xenografts formation in nude mice. And these phenotypes were attenuated by simultaneous knockdown of β-catenin with RNAi. Furthermore, we identified that FXR could bind with β-Catenin through AF1 domain, and disrupt the assembly of the core β-Catenin/TCF4 complex. Activation of FXR attenuated the DNA-binding activity of β-Catenin/TCF4, and subsequently, its targeting gene-cyclin D1 expression. Importantly, FXR expression was markedly reduced in human HCC, an event which correlated with aberrant activation of β-Catenin. These data identified FXR as a negative regulator of HCC development through direct suppression of Wnt/β-catenin pathway.
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Farnesoid X受体通过下调HER2表达抑制了他莫昔芬耐药的MCF-7乳腺癌细胞的生长。
影响因子：
8
作者：
Giordano, C.;Catalano, S.;Panza, S.;Vizza, D.;Barone, I.;Bonofiglio, D.;Gelsomino, L.;Rizza, P.;Fuqua, S. A. W.;Ando, S.
通讯作者：
Ando, S.
影响因子：
29.4
作者：
Laurent-Puig, P;Legoix, P;Zucman-Rossi, J
通讯作者：
Zucman-Rossi, J
影响因子：
--
作者：
Meyer, Mark B.;Goetsch, Paul D.;Pike, J. Wesley
通讯作者：
Pike, J. Wesley
影响因子：
28.5
作者：
Dai J;Wang H;Shi Y;Dong Y;Zhang Y;Wang J
通讯作者：
Wang J
DOI：
10.1124/jpet.111.179390
发表时间：
2011-07-01
影响因子：
3.5
作者：
Wolfe, Andy;Thomas, Ann;Apte, Udayan
通讯作者：
Apte, Udayan