YAP/TAZ at the Roots of Cancer

Cancer Cell. 2016 Jun 13;29(6):783-803. doi: 10.1016/j.ccell.2016.05.005.

Abstract

YAP and TAZ are highly related transcriptional regulators pervasively activated in human malignancies. Recent work indicates that, remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, chemoresistance, and metastasis. YAP/TAZ are sensors of the structural and mechanical features of the cell microenvironment. A number of cancer-associated extrinsic and intrinsic cues conspire to overrule the YAP-inhibiting microenvironment of normal tissues, including changes in mechanotransduction, inflammation, oncogenic signaling, and regulation of the Hippo pathway. Addiction to YAP/TAZ thus potentially represents a central cancer vulnerability that may be exploited therapeutically.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mechanotransduction, Cellular
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Neoplastic Stem Cells / metabolism
  • Phosphoproteins / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism
  • Signal Transduction
  • Transcription Factors
  • Tumor Microenvironment

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Transcription Factors
  • WWTR1 protein, human
  • YAP1 (Yes-associated) protein, human
  • Hippo protein, human
  • Protein-Serine-Threonine Kinases