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

摘要

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(MOB 1)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.