Kindlin-2 interacts with and stabilizes EGFR and is required for EGF-induced breast cancer cell migration

Cancer Letters
Baohui GuoHongquan Zhang

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.

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Citations

Jul 15, 2015·Inflammopharmacology·M AfzalM Menon
Jul 15, 2015·Journal of Biomedical Science·Eun Jeong ParkMotomu Shimaoka
Sep 3, 2017·Journal of Cell Science·Zhongji LiaoSanford J Shattil
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Nov 22, 2018·Science China. Life Sciences·Bing LiHongquan Zhang
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Nov 28, 2018·Journal of Experimental & Clinical Cancer Research : CR·Paula AzorinKeltouma Driouch
Nov 6, 2018·Cancer Cell International·Sheng LiuZengwu Shao
Apr 30, 2021·Journal of Cell Science·Wenting BuYong-Gui Gao
Apr 13, 2021·American Journal of Respiratory Cell and Molecular Biology·Robert Guzy, Elizabeth F Redente

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