Department of Urology, Tungs' Taichung MetroHarbor Hospital, Taichung 435, Taiwan.
Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan.
Int J Mol Sci. 2019 Jun 7;20(11):2792. doi: 10.3390/ijms20112792.
The prognostic and therapeutic values of fibronectin have been reported in patients with renal cell carcinoma (RCC). However, the underlying mechanisms of malignancy in RCC are not completely understood. We found that silencing of fibronectin expression attenuated human RCC 786-O and Caki-1 cell growth and migration. Silencing of potential fibronectin receptor integrin α5 and integrin β1 decreased 786-O cell ability in movement and chemotactic migration. Biochemical examination revealed a reduction of cyclin D1 and vimentin expression, transforming growth factor-β1 (TGF-β1) production, as well as Src and Smad phosphorylation in fibronectin-silenced 786-O and Caki-1 cells. Pharmacological inhibition of Src decreased 786-O cell growth and migration accompanied by a reduction of cyclin D1, fibronectin, vimentin, and TGF-β1 expression, as well as Src and Smad phosphorylation. In 786-O cells, higher activities in cell growth and migration than in Caki-1 cells were noted, along with elevated fibronectin and TGF-β1 expression. The additions of exogenous fibronectin and TGF-β1 promoted Caki-1 cell growth and migration, and increased cyclin D1, fibronectin, vimentin, and TGF-β1 expression, as well as Src and Smad phosphorylation. These findings highlight the role of fibronectin in RCC cell growth and migration involving Src and TGF-β1 signaling.
纤维连接蛋白在肾细胞癌（RCC）患者中的预后和治疗价值已有报道。然而，RCC 恶性肿瘤的潜在机制尚不完全清楚。我们发现，沉默纤维连接蛋白的表达可减弱人肾癌细胞 786-O 和 Caki-1 的生长和迁移。潜在纤维连接蛋白受体整合素 α5 和整合素 β1 的沉默降低了 786-O 细胞的运动和趋化迁移能力。生化检测显示纤维连接蛋白沉默的 786-O 和 Caki-1 细胞中细胞周期蛋白 D1 和波形蛋白表达、转化生长因子-β1（TGF-β1）产生以及Src 和 Smad 磷酸化减少。Src 的药理学抑制降低了 786-O 细胞的生长和迁移，同时伴有细胞周期蛋白 D1、纤维连接蛋白、波形蛋白和 TGF-β1 表达以及 Src 和 Smad 磷酸化减少。在 786-O 细胞中，细胞生长和迁移的活性高于 Caki-1 细胞，同时纤维连接蛋白和 TGF-β1 的表达也增加。外源性纤维连接蛋白和 TGF-β1 的添加促进了 Caki-1 细胞的生长和迁移，并增加了细胞周期蛋白 D1、纤维连接蛋白、波形蛋白和 TGF-β1 的表达，以及 Src 和 Smad 的磷酸化。这些发现强调了纤维连接蛋白在涉及 Src 和 TGF-β1 信号通路的 RCC 细胞生长和迁移中的作用。
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