Related Experiment Video

Updated: Aug 23, 2025

Live-cell Measurement of Odorant Receptor Activation Using a Real-time cAMP Assay
09:11

Live-cell Measurement of Odorant Receptor Activation Using a Real-time cAMP Assay

Published on: October 2, 2017

9.0K

The olfactory receptor OR51E2 activates ERK1/2 through the Golgi-localized Gβγ-PI3Kγ-ARF1 pathway in prostate cancer

Xin Xu1, Mostafa Khater1, Guangyu Wu1

  • 1Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA, United States.

Frontiers in Pharmacology
|October 31, 2022
PubMed

Insights

Olfactory receptor OR51E2 activation by β-ionone stimulates prostate cancer cell growth. This occurs via the Gβγ-PI3Kγ-ARF1 pathway, highlighting a new target for prostate cancer therapy.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The olfactory receptor OR51E2 is found in prostate tissues and influences prostate cancer progression.
  • Its specific role in mitogen-activated protein kinase (MAPK) pathway activation during oncogenesis is not well understood.

Purpose of the Study:

  • To investigate the function and regulation of OR51E2 in prostate cancer, particularly its role in MAPK activation.
  • To elucidate the signaling pathway downstream of OR51E2 responsible for extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation.

Main Methods:

  • Utilized β-ionone as an OR51E2 agonist to study its effects on prostate cancer cells.
  • Employed CRISPR-Cas9 gene editing to knock out key pathway components (Gγ9, PI3Kγ, ARF1).
  • Used pharmacological inhibitors for Gβγ, PI3Kγ, and Golgi-localized ARF1.
  • Assessed ERK1/2 activation and ARF1 translocation to the Golgi.

Main Results:

  • β-ionone dose-dependently activated ERK1/2 in prostate cancer cells (EC50 ≈ 20 μM).
  • Knockout or inhibition of Gγ9, PI3Kγ, or ARF1 abolished β-ionone-induced ERK1/2 activation.
  • β-ionone promoted ARF1 translocation to the Golgi and activated ARF1, effects dependent on Gγ9 and PI3Kγ.

Conclusions:

  • OR51E2 activation by β-ionone triggers ERK1/2 signaling through a Golgi-localized Gβγ-PI3Kγ-ARF1 pathway.
  • This pathway provides crucial insights into MAPK hyper-activation in prostate cancer.
  • Identifies a potential therapeutic target for managing prostate cancer progression.
Keywords:
ARF1ERK1/2G protein-coupled receptorGolgi translocationGβγPI3Kγolfactory receptor OR51E2prostate cancer

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