TGF-beta 1 modulated the expression of alpha 5 beta 1 integrin and integrin-mediated signaling in human hepatocarcinoma cells

Integrins are a family of cell surface adhesion molecules which mediate cel l adhesion and initiate signaling pathways that regulate cell spreading, mi gration, 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 inte grin on cell surface, the mRNA level of alpha 5 subunit, and subsequently s timulated 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 phosp horylation level of FAK, which can be activated by the ligation and cluster ing of integrins, PTEN can directly dephosphorylate FAK, and the results th at TGF-beta 1 could down-regulate PTEN at protein level suggested that TGF- beta 1 might stimulate FAK phosphorylation through increasing integrin sign aling and reducing dephosphorylation of FAK. These studies indicated that T GF-beta 1 and integrin-mediated signaling act synergistically to enhance ce ll adhesion and migration and affect downstream signaling molecules of hepa tocarcinoma cells. (C) 2000 Academic Press.