Reza Bayat Mokhtari, Neda Ashayeri, Leili Baghaie, Manpreet Sambi, Kosar Satari, Narges Baluch, Dmitriy A. Bosykh, Myron R. Szewczuk, Sayan Chakraborty

The Hippo Pathway Effectors YAP/TAZ-TEAD Oncoproteins as Emerging Therapeutic Targets in the Tumor Microenvironment

  • Cancer Research
  • Oncology
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Various cancer cell-associated intrinsic and extrinsic inputs act on YAP/TAZ proteins to mediate the hyperactivation of the TEAD transcription factor-based transcriptome. This YAP/TAZ-TEAD activity can override the growth-limiting Hippo tumor-suppressor pathway that maintains normal tissue homeostasis. Herein, we provide an integrated summary of the contrasting roles of YAP/TAZ during normal tissue homeostasis versus tumor initiation and progression. In addition to upstream factors that regulate YAP/TAZ in the TME, critical insights on the emerging functions of YAP/TAZ in immune suppression and abnormal vasculature development during tumorigenesis are illustrated. Lastly, we discuss the current methods that intervene with the YAP/TAZ-TEAD oncogenic signaling pathway and the emerging applications of combination therapies, gut microbiota, and epigenetic plasticity that could potentiate the efficacy of chemo/immunotherapy as improved cancer therapeutic strategies.

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