Emerging roles for the YAP/TAZ transcriptional regulators in brain tumour pathology and targeting options

Neuropathol Appl Neurobiol. 2022 Feb;48(2):e12762. doi: 10.1111/nan.12762. Epub 2021 Aug 26.

Abstract

The transcriptional co-activators Yes-associated protein 1/transcriptional co-activator with PDZ-binding motif (YAP/TAZ) have emerged as significant regulators of a wide variety of cellular and organ functions with impact in early embryonic development, especially during the expansion of the neural progenitor cell pool. YAP/TAZ signalling regulates organ size development, tissue homeostasis, wound healing and angiogenesis by participating in a complex network of various pathways. However, recent evidence suggests an association of these physiologic regulatory effects of YAP/TAZ with pro-oncogenic activities. Herein, we discuss the physiological functions of YAP/TAZ as well as the extensive network of signalling pathways that control their expression and activity, leading to brain tumour development and progression. Furthermore, we describe current targeting approaches and drug options including direct YAP/TAZ and YAP-TEA domain transcription factor (TEAD) interaction inhibitors, G-protein coupled receptors (GPCR) signalling modulators and kinase inhibitors, which may be used to successfully attack YAP/TAZ-dependent tumours.

Keywords: YAP/TAZ; brain cancer; glioma; hippo signalling pathway; neuronal progenitors; stem cells; targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Disease Progression
  • Humans
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins / metabolism*
  • YAP-Signaling Proteins / metabolism*

Substances

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