YAP-mediated induction of monoacylglycerol lipase restrains oncogenic transformation

Eric D Tang1, Cun-Yu Wang1

  • 1Laboratory of Molecular Signaling, Division of Oral Biology & Medicine, UCLA School of Dentistry, Los Angeles, CA 90095, United States.

Cellular Signalling
|February 1, 2015
PubMed

Insights

The Hippo pathway regulates growth, with YAP acting as a key coactivator. Researchers found monoacylglycerol lipase (MAGL) restrains YAP-mediated cell transformation, identifying it as a YAP target.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • The Hippo pathway is a critical regulator of cell proliferation and organ size.
  • YAP (Yes-associated protein) is a transcriptional coactivator and a key downstream effector of the Hippo pathway.
  • Aberrant YAP activity is implicated in various cancers, but the precise mechanisms of its oncogenic functions are not fully elucidated.

Purpose of the Study:

  • To investigate the mechanisms underlying the oncogenic properties of YAP.
  • To identify novel YAP transcriptional targets that modulate YAP-mediated cell growth and transformation.
  • To understand the role of YAP's transactivation domain in regulating YAP function.

Main Methods:

  • Analysis of YAP's transactivation (TA) domain function in YAP-mediated gene expression and anchorage-independent growth.
  • Identification of YAP transcriptional targets using molecular biology techniques.
  • Functional studies involving knockdown of identified targets to assess their impact on YAP-dependent cell transformation.

Main Results:

  • YAP's TA domain mediates gene expression but inhibits anchorage-independent growth.
  • Monoacylglycerol lipase (MAGL) was identified as a direct transcriptional target of YAP.
  • MAGL acts as an inhibitor of anchorage-dependent cell growth, and its knockdown enhances YAP-dependent cell transformation.

Conclusions:

  • MAGL is a novel transcriptional target of YAP that functions to restrain YAP-mediated cellular transformation.
  • The findings reveal a new regulatory mechanism where YAP can induce a target gene (MAGL) that limits its own oncogenic potential.
  • Understanding this MAGL-YAP axis may offer new therapeutic strategies for YAP-driven cancers.

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