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Insulin activates EGFR by stimulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells
Miyoung Shin1, Eun Gyeong Yang2, Hyun Kyu Song3
1Division of Life Sciences, Korea University, Seoul 136-701; Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea.
Abstract:
The expression of epidermal growth factor receptor (EGFR) is an important diagnostic marker for triple-negative breast cancer (TNBC) cells, which lack three hormonal receptors: estrogen and progesterone receptors as well as epidermal growth factor receptor 2. EGFR transactivation can cause drug resistance in many cancers including TNBC, but the mechanism underlying this phenomenon is poorly defined. Here, we demonstrate that insulin treatment induces EGFR activation by stimulating the interaction of EGFR with insulin-like growth factor receptor 1 (IGF-1R) in the MDA-MB-436 TNBC cell line. These cells express low levels of EGFR, while exhibiting high levels of IGF-1R expression and phosphorylation. Low-EGFRexpressing MDA-MB-436 cells show high sensitivity to insulinstimulated cell growth. Therefore, unexpectedly, insulin stimulation induced EGFR transactivation by regulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells.
Insights
Insulin activates epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) cells by interacting with insulin-like growth factor receptor 1 (IGF-1R). This unexpected finding sheds light on drug resistance mechanisms in TNBC.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Epidermal growth factor receptor (EGFR) is a key diagnostic marker for triple-negative breast cancer (TNBC).
- EGFR transactivation is implicated in drug resistance in various cancers, including TNBC, but the underlying mechanisms remain unclear.
- TNBC cells characteristically lack estrogen receptors, progesterone receptors, and HER2.
Purpose of the Study:
- To investigate the mechanism by which insulin induces EGFR activation in TNBC cells.
- To explore the role of insulin-like growth factor receptor 1 (IGF-1R) in EGFR transactivation within TNBC.
- To understand the implications for therapeutic resistance in low-EGFR expressing TNBC.
Main Methods:
- Utilized the MDA-MB-436 TNBC cell line, characterized by low EGFR and high IGF-1R expression.
- Administered insulin treatment to stimulate cell growth and receptor activity.
- Analyzed the interaction between EGFR and IGF-1R using molecular biology techniques.
Main Results:
- Insulin treatment stimulated EGFR activation in MDA-MB-436 cells.
- EGFR activation was mediated by the interaction between EGFR and IGF-1R.
- Low-EGFR expressing TNBC cells demonstrated significant sensitivity to insulin-stimulated growth.
Conclusions:
- Insulin induces EGFR transactivation in low-EGFR expressing TNBC cells through its interaction with IGF-1R.
- This interaction represents a novel mechanism contributing to therapeutic resistance in TNBC.
- Findings provide new insights into the complex signaling pathways driving TNBC progression and drug resistance.
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