TGF-beta 1 modulated the expression of alpha 5 beta 1 integrin and integrin-mediated signaling in human hepatocarcinoma cells

Biochem Biophys Res Commun. 2000 Aug 2;274(2):519-25. doi: 10.1006/bbrc.2000.3177.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Adhesion / drug effects
  • Cell Movement / drug effects
  • Dose-Response Relationship, Drug
  • Fibronectins / metabolism
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Gene Expression / drug effects
  • Humans
  • Laminin / metabolism
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / biosynthesis
  • Phosphorylation / drug effects
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Fibronectin / biosynthesis*
  • Receptors, Fibronectin / genetics
  • Signal Transduction / drug effects*
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*
  • Tyrosine / metabolism


  • Fibronectins
  • Laminin
  • RNA, Messenger
  • Receptors, Cell Surface
  • Receptors, Fibronectin
  • Transforming Growth Factor beta
  • Tumor Suppressor Proteins
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human