Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer |
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Affiliation: | 1. Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China;2. Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China;3. Center for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou 310058, China |
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Abstract: | 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. |
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Keywords: | YAP TAZ HIFs Hypoxia Solid tumor |
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