Xie Yiping, Qin Cheng, Zhang Xiangyu, Li Zeru, Zhao Bangbo, Li Tianyu, Zhao Yutong, Yan Yutong, Shi Haoyu, Huang Lirui, Wang Weibin
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, 100730, Beijing, PR China.
Cancer Lett. 2025 Oct 1;629:217864. doi: 10.1016/j.canlet.2025.217864. Epub 2025 Jun 6.
The Yes-associated protein (YAP) is a critical regulator of organ size and a key player in tumorigenesis, with its activity primarily governed by the Hippo signaling pathway. YAP mainly functions as a transcriptional co-activator, therefore its activity is closely related to its nuclear localization. Recent studies have shed light on mechanisms that regulate YAP's nuclear localization and activation, independent of the Hippo pathway. Beyond its role in development and tissue homeostasis, YAP's dysregulation is implicated in various cancers, including pancreatic cancer, one of the most lethal cancers. Activated YAP translocates to the nuclear of cancer cell, subsequently promotes expression of downstream genes involved in tumor growth, metastasis, and resistance to chemotherapy, etc. Moreover, YAP can also function as a transcription suppressor, indicating its context-dependent role in cancer. A thorough understanding of YAP regulation in pancreatic cancer could offer new insights for targeted therapy approaches. Here this review concludes recent findings on Hippo-independent regulation of YAP nuclear localization and the role of YAP in pancreatic cancer progression.
Yes相关蛋白（YAP）是器官大小的关键调节因子，也是肿瘤发生过程中的关键角色，其活性主要受Hippo信号通路调控。YAP主要作为转录共激活因子发挥作用，因此其活性与其核定位密切相关。最近的研究揭示了独立于Hippo通路调控YAP核定位和激活的机制。除了在发育和组织稳态中的作用外，YAP失调与包括胰腺癌在内的各种癌症有关，胰腺癌是最致命的癌症之一。激活的YAP易位至癌细胞核内，随后促进参与肿瘤生长、转移和化疗耐药等的下游基因表达。此外，YAP还可作为转录抑制因子发挥作用，表明其在癌症中具有依赖于背景的作用。深入了解胰腺癌中YAP的调控机制可为靶向治疗方法提供新见解。本文综述总结了关于YAP核定位的Hippo非依赖性调控以及YAP在胰腺癌进展中的作用的最新研究结果。
