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.

缺氧是实体瘤的共同特征。作为转录因子，缺氧诱导因子（HIFs）是缺氧微环境的主要调节因子。它们的靶基因在肿瘤发生和肿瘤发展中起作用。有趣的是，yes相关蛋白（YAP）及其具有PDZ结合基序（TAZ）的旁系同源转录共激活因子在低氧肿瘤的恶性进展中起着基本作用。作为哺乳动物Hippo途径的下游效应子，YAP和/或TAZ（YAP / TAZ）被大的抑癌激酶1/2（LATS1 / 2）-MOB激酶激活剂1（MOB1）复合物磷酸化并螯合在细胞质中，这限制了YAP / TAZ的转录活性。但是，去磷酸化的YAP / TAZ具有转位至细胞核的能力，在细胞核中它们诱导靶基因的转录，其中大多数与癌症密切相关。本文中，我们回顾了YAP / TAZ与缺氧之间与肿瘤相关的信号交互作用，描述了针对缺氧-YAP / TAZ轴的当前药物和治疗策略，并重点介绍了可能在未来产生潜在影响的问题。