Nuclear localization of YAP in pancreatic cancer: More players besides Hippo pathway

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.