S-Space College of Medicine/School of Medicine (의과대학/대학원) Molecular and Clinical Oncology (분자종양의학전공) Journal Papers (저널논문_분자종양의학전공)
TGF-beta1-mediated activations of c-Src and Rac1 modulate levels of cyclins and p27(Kip1) CDK inhibitor in hepatoma cells replated on fibronectin
- Kim, Hwang-Phill; Kim, Tai-Young; Lee, Mi-Sook; Jong, Hyun-Soon; Kim, Tae-You; Lee, Jung Weon; Bang, Yung-Jue
- Issue Date
- Biochim Biophys Acta. 2005;1743(1-2):151-61.
- Actins/metabolism; Blotting, Western; Bromodeoxyuridine/pharmacology; Carcinoma, Hepatocellular/*metabolism; Cell Adhesion; Cell Cycle; Cell Cycle Proteins/*metabolism; Cell Line; Cell Line, Tumor; Cell Proliferation; Collagen Type I/metabolism; Cyclin A/metabolism; Cyclin E/metabolism; Cyclin-Dependent Kinase Inhibitor p27; Cytoskeleton; Electrophoresis, Polyacrylamide Gel; Fibronectins/*metabolism; Flow Cytometry; Fluorescent Antibody Technique, Indirect; Gene Expression Regulation; Humans; Integrin alpha2/metabolism; Integrins/metabolism; Microscopy, Phase-Contrast; Mutation; Phosphotransferases/*metabolism; Protein Binding; Protein-Tyrosine Kinases; Proto-Oncogene Proteins/*metabolism; Signal Transduction; Transfection; Transforming Growth Factor beta/*metabolism; Transforming Growth Factor beta1; Tumor Suppressor Proteins/*metabolism; rac1 GTP-Binding Protein/*metabolism
- Integrin-mediated cell adhesion transduces signals to regulate actin cytoskeleton and cell proliferation. While understanding how integrin signals cross-talk with the TGF-beta1 pathways, we observed lamellipodia formation and cyclin regulation in Hep3B cells, following TGF-beta1 treatment. To answer if integrin signaling via actin organization might regulate cell cycle progression after TGF-beta1 treatment, we analyzed cross-talk between the two receptor-mediated pathways in hepatoma cells on specific ECMs. We found that basal and TGF-beta1-mediated activation of c-Src and Rac1, expression of cyclins E and A, and suppression of p27Kip1 were significant in cells replated on fibronectin, but not in cells on collagen I, indicating a different integrin-mediated cellular response to TGF-beta1 treatment. Levels of tyrosine phosphorylation and actin-enriched lamellipodia on fibronectin were also more prominent than in cells on collagen I. Studies using pharmacological inhibitors or transient transfections revealed that the preferential TGF-beta1 effects in cells on fibronectin required c-Src family kinase activity. These observations suggest that a specific cross-talk between TGF-beta1 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-beta1 pathways.
- 0006-3002 (Print)
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