The Ambivalent Function of YAP in Apoptosis and Cancer

Int J Mol Sci. 2018 Nov 27;19(12):3770. doi: 10.3390/ijms19123770.

Abstract

Yes-associated protein, a core regulator of the Hippo-YAP signaling pathway, plays a vital role in inhibiting apoptosis. Thus, several studies and reviews suggest that yes-associated protein is a good target for treating cancer. Unfortunately, more and more evidence demonstrates that this protein is also an essential contributor of p73-mediated apoptosis. This questions the concept that yes-associated protein is always a good target for developing novel anti-cancer drugs. Thus, the aim of this review was to evaluate the clinical relevance of yes-associated protein for cancer pathophysiology. This review also summarized the molecules, processes and drugs, which regulate Hippo-YAP signaling and discusses their effect on apoptosis. In addition, issues are defined, which should be addressed in the future in order to provide a solid basis for targeting the Hippo-YAP signaling pathway in clinical trials.

Keywords: Hippo; YAP; autophagy; cancer; cell death; p73; signaling pathway; therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis* / genetics
  • Autophagy
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Drug Discovery
  • Gene Expression Regulation
  • Glycolysis
  • Hippo Signaling Pathway
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction / drug effects
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • Nuclear Proteins
  • Transcription Factors
  • YY1AP1 protein, human
  • Protein Serine-Threonine Kinases