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

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.