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Updated: Jul 21, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
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.
Abstract:
Breast cancer is a widespread and complex disease characterized by abnormal signaling pathways that promote tumor growth and progression. Despite significant medical advances and the development of increasingly effective therapies for breast cancer, drug resistance and reduced sensitivity to prior therapies remain persistent challenges. Dysregulation of growth factors such as FGFs and EGF and their receptors is a contributing factor to reduced response to treatment, promoting cell survival and proliferation, metastasis, EMT or increased expression of ABC transporters. Our study demonstrates a protective role for FGF1 in MCF-7 breast cancer cells against taltobulin-induced cytotoxicity, mediated by activation of its receptors and compares its activity to EGF, another growth factor involved in breast cancer development and progression. The mechanisms of action of these two proteins are different: FGF1 exerts its effects through the activation of both ERKs and AKT, whereas EGF acts only through ERKs. FGF1 action in the presence of the drug promotes cell viability, reduces apoptosis and increases cell migration. Although EGF and its receptors have received more attention in breast cancer research to date, our findings highlight the key role played by FGFs and their receptors in promoting drug resistance to tubulin polymerization inhibitors in FGFR-positive tumors.
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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