Kindlin-2 与 EGFR 相互作用并使其稳定，是 EGF 诱导的乳腺癌细胞迁移所必需的。
Kindlin-2 interacts with and stabilizes EGFR and is required for EGF-induced breast cancer cell migration.
机构信息
Key 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.
Key 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.
出版信息
Cancer Lett. 2015 Jun 1;361(2):271-81. doi: 10.1016/j.canlet.2015.03.011. Epub 2015 Mar 16.
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.
表皮生长因子受体（EGFR）介导多种信号通路，调节细胞增殖、迁移和肿瘤侵袭。Kindlin-2 作为黏着斑分子，与整合素结合，控制细胞迁移和侵袭。然而，Kindlin-2 在乳腺癌进展中的作用的分子机制仍不清楚。本研究报道 Kindlin-2 与 EGFR 相互作用，介导 EGF 诱导的乳腺癌细胞迁移。研究发现，EGF 处理在多种癌细胞中均能显著增加 Kindlin-2 的 mRNA 和蛋白水平。EGFR 或 PI3K 的抑制剂特异性阻断 EGF 诱导的 Kindlin-2 表达。重要的是，Kindlin-2 与 EGFR 激酶结构域相互作用，这与 Kindlin-2 与整合素胞质结构域的结合无关。有趣的是，Kindlin-2 通过阻止 EGFR 的泛素化和降解稳定 EGFR 蛋白。Kindlin-2 的耗竭会损害 EGF 诱导的细胞迁移。本研究结果表明，Kindlin-2 参与 EGFR 信号通路并调节乳腺癌进展。
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