TGF-β1 modulated the expression of α5β1 integrin and integrin-mediated signaling in human hepatocarcinoma cells
TGF-β1 modulated the expression of α5β1 integrin and integrin-mediated signaling in human hepatocarcinoma cells
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DOI：
10.1006/bbrc.2000.3177
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发表时间：
2000-08-02
影响因子：
3.1
通讯作者：
Zha, XL
中科院分区：
文献类型：
--
作者：
Cai, T;Lei, QY;Zha, XL
整合素是一类细胞表面粘附分子，介导细胞粘附并启动调节细胞扩散、迁移、分化和增殖的信号通路。tgf - β是一种多功能因子，可诱导多种细胞过程。在这项研究中，我们发现tgf - β 1处理增加了SMMC-7721细胞表面α 5 β 1整合素的数量和α 5亚基的mRNA水平，并随后刺激细胞粘附在纤维连接蛋白（Fn）和层粘连蛋白（Ln）基质上。tgf - β 1也能促进细胞迁移。此外，我们的研究结果表明，tgf - β 1处理刺激了FAK的酪氨酸磷酸化水平，该磷酸化水平可通过整合素的连接和聚集激活，PTEN可直接使FAK去磷酸化，而tgf - β 1可在蛋白水平下调PTEN的结果表明，tgf - β 1可能通过增加整合素信号传导和减少FAK的去磷酸化来刺激FAK磷酸化。这些研究表明，tgf - β 1和整合素介导的信号传导协同作用，增强细胞粘附和迁移，并影响肝癌细胞的下游信号分子。(C) 2000年学术出版社。
Integrins are a family of cell surface adhesion molecules which mediate cell adhesion and initiate signaling pathways that regulate cell spreading, migration, differentiation, and proliferation. TGF-beta is a multifunctional factor that induces a wide variety of cellular processes. In this study, we show that, TGF-beta 1 treatment enhanced the amount of alpha 5 beta 1 integrin on cell surface, the mRNA level of alpha 5 subunit, and subsequently stimulated cell adhesion onto a fibronectin (Fn) and laminin (Ln) matrix in SMMC-7721 cells. TGF-beta 1 could also promote cell migration. Furthermore, our results showed that TGF-beta 1 treatment stimulated the tyrosine phosphorylation level of FAK, which can be activated by the ligation and clustering of integrins, PTEN can directly dephosphorylate FAK, and the results that TGF-beta 1 could down-regulate PTEN at protein level suggested that TGF-beta 1 might stimulate FAK phosphorylation through increasing integrin signaling and reducing dephosphorylation of FAK. These studies indicated that TGF-beta 1 and integrin-mediated signaling act synergistically to enhance cell adhesion and migration and affect downstream signaling molecules of hepatocarcinoma cells. (C) 2000 Academic Press.