Related Experiment Video

Updated: Aug 20, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods

Published on: July 17, 2019

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Glucocorticoid receptor and RAS: an unexpected couple in cancer

Ion C Cirstea1, Herwig P Moll2, Jan Tuckermann1

  • 1Institute of Comparative Molecular Endocrinology, University of Ulm, Helmholtzstrasse 8/1, 89081 Ulm, Germany.

Trends in Cell Biology
|November 25, 2022
PubMed

Insights

Activated rat sarcoma (RAS) GTPases drive tumor growth. Glucocorticoid receptor (GR) modulates RAS activation; unliganded GR inhibits it, while ligand-bound GR unleashes RAS signaling, impacting cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Constitutively activated rat sarcoma (RAS) GTPases are key drivers of tumor growth and challenging therapeutic targets.
  • The glucocorticoid receptor (GR) is a nuclear receptor involved in inflammation, metabolism, and cell growth regulation.

Purpose of the Study:

  • To investigate the role of the glucocorticoid receptor (GR) in modulating RAS-dependent signaling and RAS activation.
  • To explore the formation and maintenance of RAS-GR complexes for potential oncogenic RAS biology breakthroughs.

Main Methods:

  • Investigated the interaction between GR and RAS-RAF1 complexes.
  • Analyzed the effect of ligand binding on GR localization and RAS activation.

Main Results:

  • Unliganded GR decreases RAS activation.
  • Ligand binding causes GR to leave RAS complexes, translocate to the nucleus, and activate RAS pathways.
  • GR forms complexes with RAS, RAF1, and 14-3-3 proteins.

Conclusions:

  • GR plays a critical role in regulating RAS activation, offering a potential therapeutic avenue.
  • Understanding RAS-GR complex dynamics is crucial for developing novel treatments for RAS-driven cancers.
Keywords:
Ras GTPasescytoplasmic actionglucocorticoid receptortumor growth

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