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Updated: Apr 16, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Kindlin-2 interacts with and stabilizes EGFR and is required for EGF-induced breast cancer cell migration
Baohui Guo1, Jianchao Gao1, Jun Zhan1
1Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, and State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China; Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing 100191, China.
Abstract:
Epidermal growth factor receptor (EGFR) mediates multiple signaling pathways that regulate cell proliferation, migration and tumor invasion. Kindlin-2 has been known as a focal adhesion molecule that binds to integrin to control cell migration and invasion. However, molecular mechanisms underlying the role of Kindlin-2 in breast cancer progression remain elusive. Here we report that Kindlin-2 interacts with EGFR and mediates EGF-induced breast cancer cell migration. We found that EGF treatment dramatically increases Kindlin-2 expression at both mRNA and protein levels in a variety of cancer cells. Inhibitors specific for EGFR or PI3K blocked Kindlin-2 induction by EGF. Importantly, Kindlin-2 interacted with EGFR kinase domain, which was independent of Kindlin-2 binding to integrin cytoplasmic domain. Intriguingly, Kindlin-2 stabilized EGFR protein by blocking its ubiquitination and degradation. Depletion of Kindlin-2 impaired EGF-induced cell migration. Our results demonstrated that Kindlin-2 participates in EGFR signaling and regulates breast cancer progression.
Insights
Kindlin-2 interacts with Epidermal Growth Factor Receptor (EGFR) to promote breast cancer cell migration. This interaction stabilizes EGFR, enhancing its signaling and contributing to tumor progression.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Signaling
Background:
- Epidermal Growth Factor Receptor (EGFR) signaling is crucial for cell proliferation, migration, and tumor invasion.
- Kindlin-2 is a focal adhesion molecule involved in cell migration and invasion, but its role in breast cancer progression is not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms of Kindlin-2 in breast cancer progression.
- To determine if Kindlin-2 interacts with EGFR and influences EGF-induced breast cancer cell migration.
Main Methods:
- Investigated Kindlin-2 expression changes upon EGF treatment in cancer cells.
- Utilized EGFR and PI3K inhibitors to assess their effect on Kindlin-2 induction.
- Performed co-immunoprecipitation to study the interaction between Kindlin-2 and EGFR.
- Assessed the impact of Kindlin-2 depletion on EGF-induced cell migration.
Main Results:
- EGF treatment significantly increased Kindlin-2 expression at both mRNA and protein levels.
- EGFR or PI3K inhibition blocked EGF-induced Kindlin-2 upregulation.
- Kindlin-2 directly interacted with the EGFR kinase domain, independent of integrin binding.
- Kindlin-2 stabilized EGFR by preventing its ubiquitination and degradation.
- Depletion of Kindlin-2 reduced EGF-induced breast cancer cell migration.
Conclusions:
- Kindlin-2 interacts with EGFR and mediates EGF-induced breast cancer cell migration.
- Kindlin-2 stabilizes EGFR protein, suggesting a role in regulating EGFR signaling.
- Kindlin-2 plays a significant role in breast cancer progression by participating in EGFR signaling pathways.
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