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TAZ/YAP fusion proteins: mechanistic insights and therapeutic opportunities

Keith Garcia1, Anne-Claude Gingras2, Kieran F Harvey3

  • 1Department of Pathology, University of Iowa, Iowa City, IA, USA; Cancer Biology Graduate Program, University of Iowa, Iowa City, IA, USA.

Trends in Cancer
|September 12, 2022
PubMed

Insights

Hippo pathway dysregulation in cancer is common, often driven by TAZ/YAP fusion proteins. These fusions activate TEAD transcription factors, offering new therapeutic targets for difficult-to-treat cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • The Hippo pathway is frequently dysregulated in various cancers, although direct point mutations are uncommon.
  • Transcriptional co-activator with PDZ-binding motif (TAZ) and Yes-associated protein (YAP) fusion proteins are prevalent in many cancer types, representing a key activation mechanism.

Purpose of the Study:

  • To investigate the role of fusion partners in conferring oncogenic properties to TAZ/YAP fusion proteins.
  • To explore the recruitment of epigenetic modifiers by TAZ/YAP fusions.
  • To identify potential therapeutic strategies targeting the Hippo pathway.

Main Methods:

  • Analysis of TAZ/YAP fusion protein structures and functions.
  • Investigation of epigenetic modifier recruitment by fusion proteins.
  • Characterization of the resulting TEAD transcription factor-based transcriptome.

Main Results:

  • TAZ/YAP fusion proteins hyperactivate TEAD transcription factors.
  • Fusion partners confer oncogenic properties by recruiting epigenetic modifiers.
  • A hybrid TEAD-based transcriptome is promoted by these epigenetic complexes.

Conclusions:

  • TAZ/YAP fusions are a common oncogenic mechanism in cancer.
  • Epigenetic modifiers cooperating with TAZ/YAP fusions are crucial for oncogenesis.
  • Understanding these epigenetic complexes offers a therapeutic avenue for Hippo pathway-driven cancers.
Keywords:
TAZTEAD transcription factorsYAPchromatin remodelingepigeneticsfusion proteins

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