Journal
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
Volume 42, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13046-023-02704-2
Keywords
Hippo pathway; YAP/TAZ; Oncogene; Tumor suppressor; Targeted therapy
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Hippo signaling pathway plays a crucial role in organ size control by regulating cell proliferation and anti-apoptosis. Dysregulation of this pathway is implicated in cancer development and progression. YAP/TAZ are the downstream effectors of Hippo pathway, and their overexpression or activation can promote tumor initiation and progression, as well as recurrence and therapeutic resistance. However, YAP/TAZ also have tumor-suppressive functions in certain contexts, caution should be taken when targeting Hippo signaling in clinical trials.
Hippo signaling was first identified in Drosophila as a key controller of organ size by regulating cell proliferation and anti-apoptosis. Subsequent studies have shown that this pathway is highly conserved in mammals, and its dysregulation is implicated in multiple events of cancer development and progression. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) (hereafter YAP/TAZ) are the downstream effectors of the Hippo pathway. YAP/TAZ overexpression or activation is sufficient to induce tumor initiation and progression, as well as recurrence and therapeutic resistance. However, there is growing evidence that YAP/TAZ also exert a tumor-suppressive function in a context-dependent manner. Therefore, caution should be taken when targeting Hippo signaling in clinical trials in the future. In this review article, we will first give an overview of YAP/TAZ and their oncogenic roles in various cancers and then systematically summarize the tumor-suppressive functions of YAP/TAZ in different contexts. Based on these findings, we will further discuss the clinical implications of YAP/TAZ-based tumor targeted therapy and potential future directions.
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