Human telomerase reverse transcriptase is a novel target of Hippo-YAP pathway
Human telomerase reverse transcriptase is a novel target of Hippo-YAP pathway
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人端粒酶逆转录酶是Hippo-YAP通路的新靶点
DOI：
10.1096/fj.201902147r
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Cong Yu-Sheng
中科院分区：
文献类型：
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作者：
Zhang Qian;Liu Ning;Bai Junjie;Zhou Qi;Mao Jian;Xu Lu;Liu Jiang;Wei Haibin;Ren Chengcheng;Wu Xiaoying;Wang Miao;Zhao Bin;Cong Yu-Sheng
端粒酶通过维持端粒稳态在肿瘤发生中起关键作用，端粒稳态是癌症的标志。然而，端粒酶在肿瘤发生过程中被重新激活或上调的机制仍不完全清楚。在这里，我们报告了Hippo途径效应子Yes相关蛋白（雅普）调节人端粒酶逆转录酶（hTERT）的表达。雅普的异位表达或生理激活增加hTERT的表达，而雅普的敲低降低hTERT的表达。雅普通过与TEA结构域家族转录因子的相互作用与hTERT启动子结合并激活hTERT转录。此外，持续的雅普过度活化促进端粒酶活性，延长端粒长度，增加hTERT表达。此外，我们发现hTERT表达与人肝癌组织中雅普激活呈正相关。总之，我们的研究结果表明，雅普促进了hTERT的表达，这可能有助于肿瘤的进展。
Telomerase plays a pivotal role in tumorigenesis by maintaining telomere homeostasis, a hallmark of cancer. However, the mechanisms by which telomerase is reactivated or upregulated during tumorigenesis remain incompletely understood. Here, we report that the Hippo pathway effector Yes‐associated protein (YAP) regulates the expression of human telomerase reverse transcriptase (hTERT). Ectopic expression or physiological activation of YAP increaseshTERTexpression, whereas knockdown of YAP decreases the expression ofhTERT. YAP binds to thehTERTpromoter through interaction with the TEA domain family transcription factors and activateshTERTtranscription. Furthermore, sustained YAP hyperactivation promotes telomerase activity and extends telomere length, with increasedhTERTexpression. In addition, we show that hTERT expression is positively correlated with YAP activation in human liver cancer tissues. Together, our results demonstrate that YAP promoteshTERTexpression, which could contribute to tumor progression.