Loss of Dlg5 expression promotes the migration and invasion of prostate cancer cells via Girdin phosphorylation
Loss of Dlg5 expression promotes the migration and invasion of prostate cancer cells via Girdin phosphorylation
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DOI：
10.1038/onc.2014.31
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发表时间：
2014-03
期刊：
影响因子：
8
通讯作者：
Lucia Tomiyama;Takuhito Sezaki;M. Matsuo;Kazumitsu Ueda;N. Kioka
中科院分区：
文献类型：
--
作者：
Lucia Tomiyama;Takuhito Sezaki;M. Matsuo;Kazumitsu Ueda;N. Kioka
据报道，Dlg5参与了癌症的进展；然而，它在前列腺癌中的作用仍然知之甚少。在这项研究中，我们证明Dlg5在前列腺癌中经常下调。我们发现Dlg5参与了细胞迁移和癌细胞侵袭的调节。内源性Dlg5基因敲除可显著增加前列腺癌细胞的迁移和侵袭能力。我们的研究首次证明了Dlg5与肌动蛋白结合的Akt底物Girdin之间的相互作用。重要的是，我们发现在Dlg5缺失的细胞中，Akt介导的Girdin磷酸化水平(p-Girdin-Ser1416)增加。针对Girdin和Wortmannin的小干扰RNA处理可降低Girdin的磷酸化，削弱Dlg5缺失对细胞迁移的影响。综上所述，我们的发现表明Dlg5与Girdin相互作用并抑制Girdin的活性，从而抑制前列腺癌细胞的迁移。
Dlg5 has been reported to participate in cancer progression; however, its role in prostate cancer still remains poorly understood. In this study, we demonstrate that Dlg5 is frequently downregulated in prostate cancer. We show here that Dlg5 is involved in the regulation of cell migration and cancer cell invasion. Knockdown of endogenous Dlg5 markedly increased prostate cancer cell migration and invasion. Our studies, for the first time, demonstrate the interaction between Dlg5 and Girdin, an actin-binding Akt substrate. Importantly, we found that levels of Akt-mediated Girdin phosphorylation (p-Girdin-Ser1416) are increased in Dlg5-depleted cells. Small interfering RNA directed against Girdin and wortmannin treatment, which was found to reduce Girdin phosphorylation, impaired the effect of Dlg5 depletion on cell migration. Taken together, our findings demonstrate that Dlg5 interacts with and inhibits the activity of Girdin, thereby suppressing the migration of prostate cancer cells.