Abstract
Integrins are a family of cell surface adhesion molecules which mediate cell adhesion and initiate signaling pathways that regulate cell spreading, migration, 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 integrin on cell surface, the mRNA level of alpha 5 subunit, and subsequently stimulated 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-beta1 treatment stimulated the tyrosine phosphorylation level of FAK, which can be activated by the ligation and clustering of integrins. PTEN can directly dephosphorylate FAK, and the results that TGF-beta 1 could down-regulate PTEN at protein level suggested that TGF-beta 1 might stimulate FAK phosphorylation through increasing integrin signaling and reducing dephosphorylation of FAK. These studies indicated that TGF-beta 1 and integrin-mediated signaling act synergistically to enhance cell adhesion and migration and affect downstream signaling molecules of hepatocarcinoma cells.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Hepatocellular / metabolism*
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Carcinoma, Hepatocellular / pathology
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Cell Adhesion / drug effects
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Cell Movement / drug effects
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Dose-Response Relationship, Drug
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Fibronectins / metabolism
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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Gene Expression / drug effects
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Humans
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Laminin / metabolism
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Liver Neoplasms / metabolism*
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Liver Neoplasms / pathology
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PTEN Phosphohydrolase
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Phosphoric Monoester Hydrolases / biosynthesis
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Phosphorylation / drug effects
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Protein-Tyrosine Kinases / metabolism
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RNA, Messenger / metabolism
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Receptors, Cell Surface / biosynthesis
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Receptors, Fibronectin / biosynthesis*
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Receptors, Fibronectin / genetics
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Signal Transduction / drug effects*
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Transforming Growth Factor beta / metabolism*
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Transforming Growth Factor beta / pharmacology
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
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Tyrosine / metabolism
Substances
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Fibronectins
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Laminin
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RNA, Messenger
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Receptors, Cell Surface
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Receptors, Fibronectin
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Transforming Growth Factor beta
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Tumor Suppressor Proteins
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Tyrosine
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Protein-Tyrosine Kinases
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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PTK2 protein, human
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Phosphoric Monoester Hydrolases
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PTEN Phosphohydrolase
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PTEN protein, human