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TGF-β1-mediated activations of c-Src and Rac1 modulate levels of cyclins and p27Kip1 CDK inhibitor in hepatoma cells replated on fibronectin

Cited 30 time in Web of Science Cited 30 time in Scopus

Kim, Hwang-Phil; Kim, Tai-Young; Lee, Mi-Sook; Jong, Hyun-Soon; Kim, Tae-You; Lee, Jung Weon; Bang, Yung-Jue

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Biochimica et Biophysica Acta - Molecular Cell Research, Vol.1743 No.1-2, pp.151-161
integrinTGF-beta 1cyclinsignal cross-talkc-SrcRac1
Integrin-mediated cell adhesion transduces signals to regulate actin cytoskeleton and cell proliferation. While understanding how integrin signals cross-talk with the TGF-beta 1 pathways, we observed lamellipodia formation and cyclin regulation in Hep3B cells, following TGF-beta 1 treatment. To answer if integrin signaling via actin organization might regulate cell cycle progression after TGF-beta 1 treatment, we analyzed cross-talk between the two receptor-mediated pathways in hepatoma cells on specific ECMs. We found that basal and TGF-beta 1-mediated activation of c-Src and Rac 1, expression of cyclins E and A, and suppression of p27(Kip1) were significant in cells replated on fibronectin, but not in cells on collagen 1, indicating a different integrin-mediated cellular response to TGF-beta 1 I treatment. Levels of tyrosine phosphorylation and actin-enriched lamellopodia on fibronectin were also more prominent than in cells on collagen I. Studies using pharmacological inhibitors or transient transfections revealed that the preferential TGF-beta 1 effects in cells on fibronectin required c-Src family kinase activity. These observations suggest that a specific cross-talk between TGF-beta 1 and fibronectin-binding integrin signal pathways leads to the activation of c-Src/Rac1/actin-organization, leading to changes in cell cycle regulator levels in hepatoma cells. Therefore, this study represents another mechanism to regulate cell cycle regulators when integrin signaling is collaborative with TGF-beta 1 pathways. (c) 2004 Elsevier B.V. All rights reserved.
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  • Department of Medicine
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