Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer

• Published in: Acta pharmaceutica Sinica. B 2020-06, Vol.10 (6), p.947-960
• Main Authors: Zhao, Chenxi, Zeng, Chenming, Ye, Song, Dai, Xiaoyang, He, Qiaojun, Yang, Bo, Zhu, Hong
• Format: Article
• Language: English
• Subjects: HIFs; Hypoxia; Review; Solid tumor; TAZ; YAP
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2019.12.010

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 hypoxia–YAP/TAZ axis, and highlight questions that might have a potential impact in the future. This review summarizes the tumor-related signaling crosstalk between YAP/TAZ and hypoxia, describes current agents and therapeutic strategies targeting the hypoxia–YAP/TAZ axis, and highlights questions that might have a potential impact in the future. [Display omitted]