Transforming growth factor-β1 increases cell migration and β1 integrin up-regulation in human lung cancer cells

被引：49
作者：
Fong, Yi-Chin [2 ,3 ,4 ]
Hsu, Sheng-Feng [5 ]
Wu, Chien-Lin [5 ]
Li, Te-Mao [5 ]
Kao, Shung-Te [2 ,4 ]
Tsai, Fuu-Jen [6 ]
Chen, Wen-Chi [7 ]
Liu, Shan-Chi [1 ]
Wu, Chi-Ming [5 ]
Tang, Chih-Hsin [1 ]
机构：
[1] China Med Univ, Coll Med, Dept Pharmacol, Taichung, Taiwan
[2] China Med Univ, Grad Inst Chinese Med Sci, Taichung, Taiwan
[3] China Med Univ Hosp, Dept Orthopaed Surg, Taichung, Taiwan
[4] China Med Univ, Sch Chinese Med, Taichung, Taiwan
[5] China Med Univ, Grad Inst Acupuncture Sci, Taichung, Taiwan
[6] China Med Univ Hosp, Dept Pediat & Med Genet, Taichung, Taiwan
[7] China Med Univ, Grad Inst Integrated Med, Taichung, Taiwan
来源：
LUNG CANCER | 2009年 / 64卷 / 01期
关键词：
TGF-beta; 1; Lung cancer; Integrin; Migration; NF-kappa B; Akt; NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR-BETA; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; PULMONARY EPITHELIAL-CELLS; TGF-BETA; SIGNAL-TRANSDUCTION; TUMOR-CELLS; CYCLOOXYGENASE-2; EXPRESSION; INTEGRIN ALPHA-V-BETA-3;
D O I：
10.1016/j.lungcan.2008.07.010
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：13 / 21
页数：9
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