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TGF-beta1-mediated activations of c-Src and Rac1 modulate levels of cyclins and p27(Kip1) CDK inhibitor in hepatoma cells replated on fibronectin
Cited 30 time in
Web of Science
Cited 30 time in Scopus
- Authors
- Issue Date
- 2005-03-22
- Publisher
- Elsevier
- Citation
- Biochim Biophys Acta. 2005;1743(1-2):151-61.
- Keywords
- 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
- Abstract
- 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.
- ISSN
- 0006-3002 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15777850
https://hdl.handle.net/10371/22325
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