YAP and TAZ: a signalling hub of the tumour microenvironment

Nat Rev Cancer. 2019 Aug;19(8):454-464. doi: 10.1038/s41568-019-0168-y.

Abstract

YAP and TAZ are transcriptional activators pervasively induced in several human solid tumours and their functions in cancer cells are the focus of intense investigation. These studies established that YAP and TAZ are essential to trigger numerous cell-autonomous responses, such as sustained proliferation, cell plasticity, therapy resistance and metastasis. Yet tumours are complex entities, wherein cancer cells are just one of the components of a composite "tumour tissue". The other component, the tumour stroma, is composed of an extracellular matrix with aberrant mechanical properties and other cell types, including cancer-associated fibroblasts and immune cells. The stroma entertains multiple and bidirectional interactions with tumour cells, establishing dependencies essential to unleash tumorigenesis. The molecular players of such interplay remain partially understood. Here, we review the emerging role of YAP and TAZ in choreographing tumour-stromal interactions. YAP and TAZ act within tumour cells to orchestrate responses in stromal cells. Vice versa, YAP and TAZ in stromal cells trigger effects that positively feed back on the growth of tumour cells. Recognizing YAP and TAZ as a hub of the network of signals exchanged within the tumour microenvironment provides a fresh perspective on the molecular principles of tumour self-organization, promising to unveil numerous new vulnerabilities.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / physiology*
  • Animals
  • Carcinogenesis
  • Cell Adhesion
  • Cell Proliferation
  • Extracellular Matrix / metabolism
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Phenotype
  • Signal Transduction
  • Stromal Cells / metabolism
  • Trans-Activators
  • Transcription Factors / physiology*
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • Tumor Microenvironment*
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • WWTR1 protein, human
  • YAP-Signaling Proteins
  • YAP1 protein, human