Related Experiment Video

Updated: Jun 17, 2025

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

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Fibroblast growth receptor 1 is regulated by G-quadruplex in metastatic breast cancer

Hang Lin1, Muhammad Hassan Safdar1, Sarah Washburn1

  • 1Borch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN, USA.

Communications Biology
|August 9, 2024
PubMed

Insights

Targeting G-quadruplex structures in the FGFR1 promoter with CX-5461 offers a novel therapeutic strategy. This approach effectively inhibits Fibroblast Growth Factor Receptor 1 (FGFR1) expression and blocks metastatic breast cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cellular plasticity is a key challenge in treating metastatic breast cancer (MBC).
  • Fibroblast Growth Factor Receptor (FGFR) signaling drives cellular plasticity and MBC progression.
  • Existing FGFR kinase inhibitors show limitations in targeting dormant MBC cells.

Purpose of the Study:

  • To explore novel therapeutic strategies targeting FGFR1 in MBC.
  • To investigate the role of G-quadruplex structures in the FGFR1 promoter.
  • To evaluate the efficacy of G-quadruplex stabilizers in inhibiting MBC.

Main Methods:

  • Analysis of the FGFR1 proximal promoter for G-quadruplex forming sequences.
  • Circular dichroism spectroscopy to confirm G-quadruplex formation.
  • Treatment with the G-quadruplex stabilizer CX-5461 and assessment of FGFR1 expression and tumor formation.

Main Results:

  • G-quadruplex structures were identified in the FGFR1 proximal promoter.
  • CX-5461 stabilized these G-quadruplex structures.
  • CX-5461 inhibited FGFR1 promoter activity, decreased FGFR1 expression, and potently inhibited pulmonary tumor formation.

Conclusions:

  • G-quadruplex stabilization represents a promising therapeutic strategy for FGFR1-overexpressing MBC.
  • Targeting FGFR1 transcription via G-quadruplexes can overcome limitations of kinase inhibitors.
  • This approach offers a new avenue for limiting cellular plasticity in metastatic breast cancer.

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