期刊
CANCER LETTERS
卷 361, 期 1, 页码 271-281出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.03.011
关键词
Kindlin-2; Epidermal growth factor receptor; Breast cancer; Protein degradation; Cell migration
类别
资金
- Beijing Natural Science Foundation [7120002]
- National Natural Science Foundation of China [81230051, 30830048, 31170711, 81321003]
- Ministry of Science and Technology of China [2015CB553906, 2013CB910501, 2013ZX09401-004-006]
- 111 Project of the Ministry of Education
- Peking University [BMU20120314, BMU20130364]
- Leading Academic Discipline Project of Beijing Education Bureau
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 EGER 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. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据