||Chenxi Zhao, Chenming Zeng, Song Ye, Xiaoyang Dai, Qiaojun He, Bo Yang, Hong Zhu. Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer[J]. Acta Pharmaceutica Sinica B, 2020, 10(6): 947-960
|Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer
|Chenxi Zhaoa, Chenming Zenga, Song Yeb, Xiaoyang Daic, Qiaojun Hea, Bo Yanga, Hong Zhua
|a Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;
b Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China;
c Center for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou 310058, China
|Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors. As downstream effectors of the mammalian Hippo pathway, YAP and/or TAZ (YAP/TAZ) are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2 (LATS1/2)-MOB kinase activator 1 (MOB1) complex, which restricts the transcriptional activity of YAP/TAZ. However, dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes, most of which are closely related to cancer. Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia, describe current agents and therapeutic strategies targeting the hypoxiaeYAP/TAZ axis, and highlight questions that might have a potential impact in the future.
|Funds: This work was supported by National Natural Science Foundation of China (81625024 and 81773753) to Bo Yang, and Zhejiang Provincial Natural Science Foundation (LR19H310002 and LY16H310004, China) to Hong Zhu and Xiaoyang Dai, respectively.
|Corresponding author: Hong Zhu
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