The signaling network of transforming growth factor β1, protein kinase Cδ, and integrin underlies the spreading and invasiveness of gastric carcinoma cells
The signaling network of transforming growth factor β1, protein kinase Cδ, and integrin underlies the spreading and invasiveness of gastric carcinoma cells
复制标题
DOI：
10.1128/mcb.25.16.6921-6936.2005
复制
发表时间：
2005-08-01
影响因子：
5.3
通讯作者：
Lee, JW
中科院分区：
文献类型：
--
作者：
Lee, MS;Kim, TY;Lee, JW
整合素介导的细胞黏附和扩散使细胞能够对细胞外刺激做出反应以实现细胞功能。利用通常为圆形的黏附的胃癌细胞系，我们探索了细胞扩散过程的机制，分离出黏附，以及该过程的生物学后果。细胞通过整合素-细胞外基质相互作用与Smad介导的转化生长因子β1(TGFβ1)途径的协同作用而表现出扩散行为，该途径由蛋白激酶C Delta(PKC Delta)介导。在细胞外基质上复制的细胞经转化生长因子β1处理后，PKC Delta表达和磷酸化，这是整合素表达和激活所必需的。整合素α2和α3的高表达与粘着斑分子的扩散和激活有关。Smad3而不是Smad2的过表达增强了转化生长因子β1的作用。此外，转化生长因子β1治疗和PKC Delta活性需要增加对纤维连接蛋白的运动和通过Matrigel的侵袭，这表明它们与扩散行为有关。总之，这项研究清楚地证明，信号网络，包括Smad依赖的转化生长因子β途径，PKC Delta的表达和磷酸化，以及整合素的表达和激活，调节着SNU16mAd胃癌细胞变体的细胞扩散、运动和侵袭。
Integrin-mediated cell adhesion and spreading enables cells to respond to extracellular stimuli for cellular functions. Using a gastric carcinoma cell line that is usually round in adhesion, we explored the mechanisms underlying the cell spreading process, separate from adhesion, and the biological consequences of the process. The cells exhibited spreading behavior through the collaboration of integrin-extracellular matrix interaction with a Smad-mediated transforming growth factor PI (TGF beta 1) pathway that is mediated by protein kinase C delta (PKC delta). TGF beta 1 treatment of the cells replated on extracellular matrix caused the expression and phosphorylation of PKC delta, which is required for expression and activation of integrins. Increased expression of integrins alpha 2 and alpha 3 correlated with the spreading, functioning in activation of focal adhesion molecules. Smad3, but not Smad2, overexpression enhanced the TGF beta 1 effects. Furthermore, TGF beta 1 treatment and PKC delta activity were required for increased motility on fibronectin and invasion through matrigel, indicating their correlation with the spreading behavior. Altogether, this study clearly evidenced that the signaling network, involving the Smad-dependent TGF beta pathway, PKC delta expression and phosphorylation, and integrin expression and activation, regulates cell spreading, motility, and invasion of the SNU16mAd gastric carcinoma cell variant.