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Updated: May 21, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

FGFR1 cleavage and nuclear translocation regulates breast cancer cell behavior

Athina-Myrto Chioni1, Richard Grose

  • 1Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, England, UK.

The Journal of Cell Biology
|June 6, 2012
PubMed

Insights

Fibroblast growth factor receptor 1 (FGFR1) is cleaved by Granzyme B (GrB) and moves to the nucleus, regulating genes involved in breast cancer cell migration. Blocking GrB inhibits this process, offering a potential therapeutic target for invasive breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Fibroblast growth factor (FGF) signaling, particularly involving FGF-10 and its receptors FGFR1 and FGFR2, is linked to breast cancer development.
  • Breast cancer cells may exploit FGF signaling pathways for tumor progression.

Purpose of the Study:

  • To elucidate a novel downstream pathway of FGFR1 activation in breast cancer.
  • To identify the protease responsible for FGFR1 cleavage and its role in receptor trafficking.
  • To investigate the functional consequences of FGFR1 nuclear localization on cancer cell behavior and identify target genes.

Main Methods:

  • Investigated FGFR1 activation, cleavage, and nuclear translocation.
  • Utilized Granzyme B (GrB) inhibition assays to assess its role in FGFR1 trafficking.
  • Examined the effect of blocking GrB on FGF-stimulated cell migration.
  • Validated findings in clinical breast cancer samples and a 3D cancer model.
  • Identified FGFR1 target genes using molecular techniques.

Main Results:

  • A novel pathway was identified where activated FGFR1 is cleaved and traffics to the nucleus.
  • Granzyme B (GrB) was confirmed as the protease responsible for FGFR1 cleavage.
  • Inhibition of GrB blocked FGFR1 nuclear translocation and abrogated the promigratory effect of FGF.
  • Nuclear localization of FGFR1 was observed specifically in invading cells in clinical and model systems.
  • Specific target genes regulated by nuclear FGFR1 were identified, influencing cell migration.

Conclusions:

  • A novel mechanism of FGF signaling regulation involving FGFR1 cleavage and nuclear translocation has been discovered.
  • This pathway, mediated by Granzyme B, plays a significant role in promoting breast cancer cell invasion.
  • The identified FGFR1-regulated genes may constitute an invasive signature for breast cancer.
  • This pathway presents a potential novel therapeutic target for treating invasive breast cancer.

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