Related Experiment Video

Updated: Jun 26, 2025

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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The landscape of cancer-rewired GPCR signaling axes

Chakit Arora1, Marin Matic1, Luisa Bisceglia1

  • 1Laboratorio di Biologia Bio@SNS, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56126 Pisa, Italy.

Cell Genomics
|May 9, 2024
PubMed

Insights

This study reveals G-protein-coupled receptor (GPCR) ligand systems dysregulated in cancer, identifying potential therapeutic targets. Targeting these GPCR axes, including neurotransmitter pathways, shows promise for novel oncology treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • G-protein-coupled receptors (GPCRs) are crucial cell surface receptors involved in numerous physiological processes.
  • Dysregulation of GPCR signaling pathways is implicated in various cancers, representing potential therapeutic targets.
  • Understanding GPCR ligand system interactions is key to developing novel cancer therapies.

Purpose of the Study:

  • To explore the dysregulation of GPCR ligand systems in cancer transcriptomics data.
  • To identify novel therapeutic opportunities in oncology by analyzing GPCR networks.
  • To investigate the association of GPCR network alterations with cancer subtypes and patient survival.

Main Methods:

  • Analysis of cancer transcriptomics datasets to derive GPCR-ligand-enzyme interaction networks.
  • Identification of differentially regulated GPCRs and their partners across cancer subtypes.
  • Correlation analysis of GPCR network expression with transcriptional programs and patient survival.
  • Validation of drug efficacy against identified GPCR targets in cancer cell line screens.

Main Results:

  • Multiple GPCRs and their interacting partners are differentially regulated across cancer subtypes.
  • GPCR network alterations are linked to specific transcriptional programs and patient survival outcomes.
  • Combined expression of receptor-ligand/enzyme partners enhances patient stratification.
  • Identified actionable GPCR axes, including those involving neurotransmitter pathways, targeted by existing drugs with anti-cancer effects.

Conclusions:

  • GPCR ligand systems are significantly dysregulated in cancer, offering new therapeutic avenues.
  • Targeting specific GPCR axes, particularly those involving neurotransmitter pathways, demonstrates anti-cancer potential.
  • The developed webapp provides a valuable resource for exploring GPCR-cancer interactions and therapeutic targets.
Keywords:
GPCRcancercancer cell linescell-cell communicationdrug repurposingpersonalized medicinesignaling networksurvival analysistranscriptomics

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