Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
Institute of Digestive Disease, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Hong Kong, SAR, People's Republic of China.
Int J Cancer. 2023 Feb 15;152(4):558-571. doi: 10.1002/ijc.34249. Epub 2022 Aug 29.
Accumulating evidence has underscored the importance of the Hippo-YAP1 signaling in lung tissue homeostasis, whereas its deregulation induces tumorigenesis. YAP1 and its paralog TAZ are the key downstream effectors tightly controlled by the Hippo pathway. YAP1/TAZ exerts oncogenic activities by transcriptional regulation via physical interaction with TEAD transcription factors. In solid tumors, Hippo-YAP1 crosstalks with other signaling pathways such as Wnt/β-catenin, receptor tyrosine kinase cascade, Notch and TGF-β to synergistically drive tumorigenesis. As YAP1/TAZ expression is significantly correlated with unfavorable outcomes for the patients, small molecules have been developed for targeting YAP1/TAZ to get a therapeutic effect. In this review, we summarize the recent findings on the deregulation of Hippo-YAP1 pathway in nonsmall cell lung carcinoma, discuss the molecular mechanisms of its dysregulation in leading to tumorigenesis, explore the therapeutic strategies for targeting YAP1/TAZ, and provide the research directions for deep investigation. We believe that detailed delineation of Hippo-YAP1 regulation in tumorigenesis provides novel insight for accurate therapeutic intervention.
越来越多的证据强调了 Hippo-YAP1 信号通路在肺组织稳态中的重要性，而其失调会导致肿瘤发生。YAP1 和其同源物 TAZ 是受 Hippo 通路严格调控的关键下游效应物。YAP1/TAZ 通过与 TEAD 转录因子的物理相互作用进行转录调控，发挥致癌活性。在实体肿瘤中，Hippo-YAP1 与其他信号通路（如 Wnt/β-catenin、受体酪氨酸激酶级联、Notch 和 TGF-β）相互作用，协同促进肿瘤发生。由于 YAP1/TAZ 的表达与患者的不良预后显著相关，因此已经开发出针对 YAP1/TAZ 的小分子药物来获得治疗效果。在这篇综述中，我们总结了 Hippo-YAP1 通路在非小细胞肺癌中失调的最新发现，讨论了其失调导致肿瘤发生的分子机制，探讨了针对 YAP1/TAZ 的治疗策略，并为深入研究提供了研究方向。我们相信，详细阐述 Hippo-YAP1 在肿瘤发生中的调控为精确的治疗干预提供了新的见解。
