MAF1 suppresses AKT-mTOR signaling and liver cancer through activation of PTEN transcription.
MAF1 suppresses AKT-mTOR signaling and liver cancer through activation of PTEN transcription.
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MAF1 通过激活 PTEN 转录抑制 AKT-mTOR 信号传导和肝癌
DOI：
10.1002/hep.28507
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发表时间：
2016-06
期刊：
影响因子：
13.5
通讯作者：
Zheng, X. F. Steven
中科院分区：
文献类型：
--
作者：
Li, Yue;Tsang, Chi Kwan;Wang, Suihai;Li, Xiao-Xing;Yang, Yang;Fu, Liwu;Huang, Wenlin;Li, Ming;Wang, Hui-Yun;Zheng, X. F. Steven
磷脂酰肌醇3 -激酶/磷脂酰肌醇3,4,5 -三磷酸3 -磷酸酶/蛋白激酶B/哺乳动物雷帕霉素靶点（PI3K - PTEN - AKT - mTOR）通路是细胞生长的中心控制器，也是人类癌症的关键驱动因素。MAF1是mTOR下游效应因子和核糖体和转移RNA基因的转录抑制因子。肝细胞癌中MAF1表达明显降低，与疾病进展和预后不良相关。在体内和体外肿瘤模型中，MAF1均表现出肿瘤抑制活性。令人惊讶的是，阻断核糖体和转移rna的合成不足以解释MAF1的肿瘤抑制功能。相反，MAF1下调矛盾地导致AKT - mTOR信号的激活，这是由PTEN表达减少介导的。MAF1结合PTEN启动子，增强PTEN启动子乙酰化和活性。结论：与其作为转录抑制因子的典型功能相反，MAF1还可以作为PTEN的转录激活因子，这对于MAF1的肿瘤抑制功能很重要。这些结果对肝癌的疾病分期、预后预测和AKT - mTOR靶向治疗具有重要意义。(肝脏病学2016;63:1928公/ 1942)
The phosphatidylinositol 3‐kinase/phosphatidylinositol 3,4,5‐trisphosphate 3‐phosphatase/protein kinase B/mammalian target of rapamycin (PI3K‐PTEN‐AKT‐mTOR) pathway is a central controller of cell growth and a key driver for human cancer. MAF1 is an mTOR downstream effector and transcriptional repressor of ribosomal and transfer RNA genes. MAF1 expression is markedly reduced in hepatocellular carcinomas, which is correlated with disease progression and poor prognosis. Consistently, MAF1 displays tumor‐suppressor activity toward in vitro and in vivo cancer models. Surprisingly, blocking the synthesis of ribosomal and transfer RNAs is insufficient to account for MAF1's tumor‐suppressor function. Instead, MAF1 down‐regulation paradoxically leads to activation of AKT‐mTOR signaling, which is mediated by decreased PTEN expression. MAF1 binds to the PTEN promoter, enhancing PTEN promoter acetylation and activity. Conclusion: In contrast to its canonical function as a transcriptional repressor, MAF1 can also act as a transcriptional activator for PTEN, which is important for MAF1's tumor‐suppressor function. These results have implications in disease staging, prognostic prediction, and AKT‐mTOR‐targeted therapy in liver cancer. (Hepatology 2016;63:1928‐1942)
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DOI：
10.4161/cc.9.5.10876
发表时间：
2010-03-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Tsang CK;Liu H;Zheng XF
通讯作者：
Zheng XF
影响因子：
16
作者：
Roberts, Douglas N.;Wilson, Boris;Cairns, Bradley R.
通讯作者：
Cairns, Bradley R.
MAF1是PTEN和PI3K信号的新靶标，可负调节肿瘤发生和脂质代谢。
影响因子：
4.5
作者：
Palian BM;Rohira AD;Johnson SA;He L;Zheng N;Dubeau L;Stiles BL;Johnson DL
通讯作者：
Johnson DL
影响因子：
4.8
作者：
Desai, N;Lee, JH;Willis, IM
通讯作者：
Willis, IM
影响因子：
50.3
作者：
Thomas JD;Zhang YJ;Wei YH;Cho JH;Morris LE;Wang HY;Zheng XF
通讯作者：
Zheng XF