Jiang Ping, Enomoto Atsushi, Jijiwa Mayumi, Kato Takuya, Hasegawa Taisaku, Ishida Maki, Sato Tomoko, Asai Naoya, Murakumo Yoshiki, Takahashi Masahide
Department of Pathology, Center for Neurological Disease and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Cancer Res. 2008 Mar 1;68(5):1310-8. doi: 10.1158/0008-5472.CAN-07-5111.
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 line 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.
Girdin（肌动蛋白丝的大梁蛋白）是一种新型的肌动蛋白结合Akt底物，在成纤维细胞的肌动蛋白组织和Akt依赖性细胞运动中发挥重要作用。在此，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，并且通过胰岛素样生长因子（IGF-I）的刺激而发生磷酸化。体外迁移和侵袭试验表明，Girdin是MDA-MB-231细胞依赖IGF-I的细胞运动所必需的。针对Girdin的短发夹干扰RNA显著抑制了皮下移植的MDA-MB-231细胞在裸鼠中的转移。此外，Girdin在包括乳腺癌、结肠癌、肺癌和子宫颈癌在内的多种人类恶性组织中高表达。这些发现突出了Girdin在Akt信号通路异常激活的肿瘤进展中的重要作用。
