Transforming growth factor-β1 increases cell migration and β1 integrin up-regulation in human lung cancer cells
Transforming growth factor-β1 increases cell migration and β1 integrin up-regulation in human lung cancer cells
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DOI：
10.1016/j.lungcan.2008.07.010
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发表时间：
2009-04-01
期刊：
影响因子：
5.3
通讯作者：
Tang, Chih-Hsin
中科院分区：
文献类型：
--
作者：
Fong, Yi-Chin;Hsu, Sheng-Feng;Tang, Chih-Hsin
转化生长因子-β 1（Transforming growth factor-beta 1，TCF-β 1）在肿瘤细胞的粘附和迁移过程中起着重要作用。此外，整合素是哺乳动物细胞中主要的粘附分子。在这里，我们发现TGF-β 1增加了人肺癌细胞（A549细胞）中β 1整合素的迁移和细胞表面表达。TGF-β 1刺激增加了磷脂酰肌醇3-激酶（PI 3 K）的p85 α亚基和Akt的Ser（473）的磷酸化。此外，我们发现PI 3 K抑制剂Ly 294002或Akt抑制剂可抑制TGF-β 1诱导的A549细胞迁移活性。用NF-κ B抑制剂（PDTC）或I κ B蛋白酶抑制剂（TPCK）处理A549细胞也抑制TGF-β 1诱导的细胞迁移和β 1整合素表达。此外，用TGF-β 1处理A549细胞可诱导I kappa B激酶α/β（IKK α/β）磷酸化、I kappa B磷酸化、p65 Ser（536）磷酸化和kappa B-荧光素酶活性。此外，TGF-β 1介导的IKK α/β、I κ B α磷酸化和p65 Ser（536）磷酸化的增加被Ly 294002和Akt抑制剂抑制。用p85 α和Akt突变体共转染也降低了TGF-β 1诱导的κ B-荧光素酶活性。综上所述，我们的研究结果表明，TGF-β 1通过PI 3 K/Akt起作用，PI 3 K/Akt反过来激活IKK α/β和NF-κ B，导致β 1整合素的激活并促进人肺癌细胞的迁移。(C)2008爱思唯尔爱尔兰有限公司保留所有权利。
Transforming growth factor-beta 1 (TCF-beta 1) plays a crucial role in adhesion and migration of human cancer cells. Besides, integrins are the major adhesive molecules in mammalian cells. Here we found that TGF-beta 1 increased the migration and cell surface expression of beta 1 integrin in human lung cancer cells (A549 cells). TGF-beta 1 stimulation increased phosphorylation of p85 alpha subunit of phosphatidylinositol 3-kinase (PI3K) and Ser(473) of Akt was determined. Besides, we performed that PI3K inhibitor (Ly294002) or Akt inhibitor suppressed the TGF-beta 1-induced migration activities of A549 cells. Treatment of A549 cells with NF-kappa B inhibitor (PDTC) or I kappa B protease inhibitor (TPCK) also repressed TGF-beta 1-induced cells migration and beta 1 integrins expression. In addition, treatment of A549 cells with TGF-beta 1-induced I kappa B kinase alpha/beta (IKK alpha/beta) phosphorylation, I kappa B phosphorylation, p65 Ser(536) phosphorylation, and kappa B-luciferase activity. Furthermore, the TGF-beta 1-mediated increases in IKK alpha/beta, I kappa B alpha phosphorylation and p65 Ser(536) phosphorylation were inhibited by Ly294002 and Akt inhibitor. Co-transfection with p85 alpha and Akt mutants also reduced the TGF-beta 1-induced kappa B-luciferase activity. Taken together, Our results suggest that TGF-beta 1 acts through PI3K/Akt, which in turn activates IKK alpha/beta and NF-kappa B, resulting in the activations of beta 1 integrins and contributing the migration of human lung cancer cells. (C) 2008 Elsevier Ireland Ltd. All rights reserved.