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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 29 time in Web of Science Cited 28 time in Scopus
Authors
Kim, Hwang-Phill; Kim, Tai-Young; Lee, Mi-Sook; Jong, Hyun-Soon; Kim, Tae-You; Lee, Jung Weon; Bang, Yung-Jue
Issue Date
2005-03-22
Publisher
Elsevier
Citation
Biochim Biophys Acta. 2005;1743(1-2):151-61.
Keywords
Actins/metabolismBlotting, WesternBromodeoxyuridine/pharmacologyCarcinoma, Hepatocellular/*metabolismCell AdhesionCell CycleCell Cycle Proteins/*metabolismCell LineCell Line, TumorCell ProliferationCollagen Type I/metabolismCyclin A/metabolismCyclin E/metabolismCyclin-Dependent Kinase Inhibitor p27CytoskeletonElectrophoresis, Polyacrylamide GelFibronectins/*metabolismFlow CytometryFluorescent Antibody Technique, IndirectGene Expression RegulationHumansIntegrin alpha2/metabolismIntegrins/metabolismMicroscopy, Phase-ContrastMutationPhosphotransferases/*metabolismProtein BindingProtein-Tyrosine KinasesProto-Oncogene Proteins/*metabolismSignal TransductionTransfectionTransforming Growth Factor beta/*metabolismTransforming Growth Factor beta1Tumor Suppressor Proteins/*metabolismrac1 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

http://hdl.handle.net/10371/22325
DOI
https://doi.org/10.1016/j.bbamcr.2004.09.014
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College of Medicine/School of Medicine (의과대학/대학원)Molecular and Clinical Oncology (분자종양의학전공)Journal Papers (저널논문_분자종양의학전공)
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