An actin-binding protein girdin regulates the motility of breast cancer cells
An actin-binding protein girdin regulates the motility of breast cancer cells
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DOI：
10.1158/0008-5472.can-07-5111
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发表时间：
2008-03-01
期刊：
影响因子：
11.2
通讯作者：
Takahashi, Masahide
中科院分区：
文献类型：
--
作者：
Jiang, Ping;Enomoto, Atsushi;Takahashi, Masahide
Girdin（肌动蛋白纤维束）是一种新型的肌动蛋白结合Akt底物，在成纤维细胞中的肌动蛋白组织和Akt依赖的细胞运动中起重要作用。在这里，我们发现Girdin在多种癌细胞系中表达，包括乳腺癌细胞系MDA-MB-231，并且在胰岛素样生长因子（IGF-I）的刺激下被磷酸化。体外迁移和侵袭实验表明，Girdin是MDA-MB-231细胞IGF-I依赖性细胞运动所必需的。针对Girdin的短发夹状干扰RNA显著抑制肿瘤皮下转移。MDA-MB-231细胞移植于裸鼠体内。此外，Girdin在多种人类恶性组织中高度表达，包括乳腺癌、结肠癌、肺癌和宫颈癌。这些发现强调了Girdin在Akt信号通路异常激活的肿瘤进展中的重要作用。
Girdin (girders of actin filaments) is a novel actin-binding Akt substrate that plays an important role in actin organization and Akt-dependent cell motility in fibroblasts. Here, we find that Girdin is expressed in a variety of cancer cell lines, including the breast cancer cell tine MDA-MB-231, and is phosphorylated by the stimulation of insulin-like growth factor (IGF-I). In vitro migration and invasion assays showed that Girdin is required for the IGF-I-dependent cell movement of MDA-MB-231 cells. Short hairpin interfering RNA directed against Girdin markedly inhibited the metastasis of s.c. transplanted MDA-MB-231 cells in nude mice. In addition, Girdin is highly expressed in a variety of human malignant tissues, including breast, colon, lung, and uterine cervical carcinomas. These findings highlight the important role of Girdin in tumor progression in which the Akt signaling pathway is aberrantly activated.