FGF1 Protects MCF-7 Cells against Taltobulin through Both the MEKs/ERKs and PI3K/AKT Signaling Pathway

Jakub Szymczyk1, Aleksandra Czyrek2, Jacek Otlewski1

  • 1Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Joliot-Curie 14a, 50-383 Wroclaw, Poland.

Biomedicines
|July 29, 2023
PubMed

Insights

Fibroblast Growth Factor 1 (FGF1) protects breast cancer cells from a specific drug by activating its receptors, unlike Epidermal Growth Factor (EGF). This finding is crucial for understanding and overcoming drug resistance in FGFR-positive tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Breast cancer drug resistance is a major clinical challenge.
  • Growth factor dysregulation, including FGFs and EGF, contributes to treatment failure.
  • Understanding resistance mechanisms is vital for developing effective therapies.

Purpose of the Study:

  • To investigate the protective role of FGF1 against taltobulin-induced cytotoxicity in breast cancer cells.
  • To compare the mechanisms of action of FGF1 and EGF in mediating drug resistance.
  • To highlight the significance of FGFs and their receptors in overcoming resistance to tubulin inhibitors.

Main Methods:

  • Utilized MCF-7 breast cancer cell line.
  • Assessed cytotoxicity of taltobulin in the presence of FGF1 and EGF.
  • Investigated signaling pathways including ERKs and AKT activation.
  • Evaluated effects on cell viability, apoptosis, and migration.

Main Results:

  • FGF1 demonstrated a protective effect against taltobulin, enhancing cell viability and migration while reducing apoptosis.
  • FGF1-mediated protection involved activation of both ERKs and AKT pathways.
  • EGF also conferred protection but acted solely through the ERKs pathway.
  • These findings indicate distinct mechanisms for FGF1 and EGF in drug resistance.

Conclusions:

  • FGF1 plays a significant role in conferring resistance to tubulin polymerization inhibitors in FGFR-positive breast cancer.
  • The distinct signaling pathways activated by FGF1 (ERK/AKT) versus EGF (ERK) have implications for therapeutic strategies.
  • Targeting FGF signaling could be a potential approach to overcome drug resistance in specific breast cancer subtypes.

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