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TGF-beta1 (transforming growth factor-beta1)-mediated adhesion of gastric carcinoma cells involves a decrease in

Hwang-Phill Kim1, Mi-Sook Lee, Jiyon Yu

  • 1Cancer Research Institute, Department of Tumor Biology, College of Medicine, Seoul National University, 28, Yongon-Dong, Chongno-Gu, Seoul 110-799, South Korea.

The Biochemical Journal
|January 15, 2004
PubMed

Insights

Transforming growth factor beta1 (TGF-β1) induces gastric cancer cells to adhere by upregulating integrin alpha3 and decreasing Ras/ERK signaling via c-Src kinase. This reveals a novel mechanism for TGF-β1 in cell anchorage and cancer progression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Integrin-mediated cell anchorage to extracellular matrix proteins is crucial for regulating various cellular processes.
  • Transforming growth factor beta1 (TGF-β1) can alter cell adhesion properties, particularly in cancer.
  • Understanding the cross-talk between integrin and TGF-β1 signaling pathways is essential for deciphering TGF-β1's effects on cell behavior.

Purpose of the Study:

  • To investigate the molecular mechanisms by which TGF-β1 induces cell adhesion in anchorage-independent gastric carcinoma cells.
  • To elucidate the role of integrin subunits and signaling pathways, including c-Src and Ras/ERK, in TGF-β1-mediated cell adhesion.

Main Methods:

  • Utilized an anchorage-independent gastric carcinoma cell line (SNU16) and its adherent variant (SNU16Ad).
  • Analyzed changes in integrin subunit expression (integrin α3, integrin α5) upon TGF-β1 treatment.
  • Assessed signaling pathway activation, including c-Src phosphorylation, Ras-GTP loading, and ERK1/ERK2 activity, using Western blotting and pharmacological inhibitors.

Main Results:

  • TGF-β1 treatment increased cell adhesion in SNU16 and SNU16Ad cells, mediated by upregulated integrin α3.
  • TGF-β1 treatment of SNU16Ad cells on fibronectin led to increased c-Src phosphorylation and decreased Ras-GTP loading and ERK1/ERK2 activity.
  • Inhibition of ERK1/ERK2 activity slightly enhanced TGF-β1-mediated adhesion, while c-Src family kinase activity and reduced Ras/ERK signaling were critical for TGF-β1 effects.

Conclusions:

  • TGF-β1 induces adhesion in anchorage-independent gastric carcinoma cells through increased integrin α3 levels.
  • A decrease in Ras/ERK cascade activity, dependent on c-Src family kinase activity, is essential for TGF-β1-mediated cell adhesion.
  • These findings highlight a novel signaling mechanism by which TGF-β1 promotes cell adhesion in gastric cancer.

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