Related Experiment Video

Updated: Feb 16, 2026

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies
09:01

Cancer-Associated Fibroblasts from Mouse Mammary Tumors as Tools for Molecular and Computational Studies

Published on: July 3, 2025

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Unique signalling connectivity of FGFR3-TACC3 oncoprotein revealed by quantitative phosphoproteomics and differential

Benedetta Lombardi1,2, Paul Ashford2, Aurelio A Moya-Garcia2

  • 1Proteomics and Molecular Cell Dynamics, Center for Nephrology, School of Life and Medical Sciences, University College London, London NW3 2PF, United Kingdom.

Oncotarget
|December 22, 2017
PubMed

Insights

The FGFR3-TACC3 fusion drives cancer by altering cell signaling pathways, distinct from normal FGFR3. This study reveals specific pathways involved in cancer development, including stress response and TP53 regulation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • The FGFR3-TACC3 fusion oncogene drives various cancers, notably bladder cancer, through increased tyrosine kinase activity.
  • Understanding the downstream signaling of FGFR3-TACC3 is crucial for targeted cancer therapies.

Purpose of the Study:

  • To investigate the distinct downstream signaling properties of the FGFR3-TACC3 fusion compared to wild-type FGFR3.
  • To identify specific signaling pathways regulated by FGFR3-TACC3 in cancer development.

Main Methods:

  • Utilized telomerase-immortalized human urothelial cell lines expressing FGFR3-TACC3 or wild-type FGFR3.
  • Employed quantitative proteomics with isobaric tandem mass tags and phosphopeptide enrichment.
  • Applied liquid chromatography-high mass accuracy tandem mass spectrometry (LC-MS/MS) for phosphoproteomic analysis.
  • Developed and utilized the Disease Relevant Analysis of Genes On Networks (DRAGON) bioinformatics protocol.

Main Results:

  • Identified approximately 200 regulated phosphosites upon stimulation.
  • Discovered 9 pathways uniquely regulated by the FGFR3-TACC3 fusion.
  • Identified 5 pathways uniquely regulated by wild-type FGFR3 stimulation.
  • Highlighted pathways related to chaperone activation, stress response, and TP53 regulation in FGFR3-TACC3 signaling.

Conclusions:

  • The FGFR3-TACC3 fusion uniquely alters cellular signaling networks compared to wild-type FGFR3.
  • Specific pathways identified, including stress response and TP53 regulation, are implicated in cancer development and maintenance.
  • Findings provide insights into the oncogenic mechanisms of FGFR3-TACC3 and potential therapeutic targets.
Keywords:
FGFR-TACC-fusioncancernetwork analysisquantitative phosphoproteomicssignaling pathways

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