Role of YAP/TAZ transcriptional regulators in resistance to anti-cancer therapies

Cell Mol Life Sci. 2017 Apr;74(8):1457-1474. doi: 10.1007/s00018-016-2412-x. Epub 2016 Nov 8.

Abstract

A diverse range of drug resistance mechanisms in cancer cells and their microenvironment significantly reduces the effectiveness of anti-cancer therapies. Growing evidence suggests that transcriptional effectors of the Hippo pathway, YAP and TAZ, promote resistance to various anti-cancer therapies, including cytotoxic chemotherapy, molecular targeted therapy, and radiation therapy. Here, we overview the role of YAP and TAZ as drug resistance mediators, and also discuss potential upstream regulators and downstream targets of YAP/TAZ in cancer. The widespread involvement of YAP and TAZ in resistance mechanisms suggests that therapeutic targeting of YAP and TAZ may expedite the development of effective anti-resistance therapies.

Keywords: Biomarker; Drug; Hippo pathway; Resistance; TAZ; YAP.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Drug Discovery
  • Drug Resistance, Neoplasm* / drug effects
  • Hippo Signaling Pathway
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / radiotherapy
  • Phosphoproteins / metabolism*
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction / drug effects
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • WWTR1 protein, human
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Protein Serine-Threonine Kinases