The YAP/TAZ Signaling Pathway in the Tumor Microenvironment and Carcinogenesis: Current Knowledge and Therapeutic Promises

Int J Mol Sci. 2021 Dec 31;23(1):430. doi: 10.3390/ijms23010430.

Abstract

The yes-associated protein (YAP) and the transcriptional coactivator with PDZ-binding motif (TAZ) are transcriptional coactivators, members of the Hippo signaling pathway, which play a critical role in cell growth regulation, embryonic development, regeneration, proliferation, and cancer origin and progression. The mechanism involves the nuclear binding of the un-phosphorylated YAP/TAZ complex to release the transcriptional enhanced associate domain (TEAD) from its repressors. The active ternary complex is responsible for the aforementioned biological effects. Overexpression of YAP/TAZ has been reported in cancer stem cells and tumor resistance. The resistance involves chemotherapy, targeted therapy, and immunotherapy. This review provides an overview of YAP/TAZ pathways' role in carcinogenesis and tumor microenvironment. Potential therapeutic alternatives are also discussed.

Keywords: Hippo signaling pathway; TEAD; YAP/TAZ; carcinogenesis; cell proliferation; chemoresistance; drug resistance; immunotherapy; neoplastic stem cells; tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology*
  • Drug Resistance, Neoplasm
  • Humans
  • Mechanotransduction, Cellular
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins / metabolism*
  • Tumor Microenvironment*
  • YAP-Signaling Proteins*

Substances

  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • YAP-Signaling Proteins