Influence of CXCR4/SDF-1 axis on E-cadherin/β-catenin complex expression in HT29 colon cancer cells

World J Gastroenterol. 2011 Feb 7;17(5):625-32. doi: 10.3748/wjg.v17.i5.625.

Abstract

Aim: To study the influence of CXCR4/stromal cell-derived factor-1 (SDF-1) axis on E-cadherin/β-catenin complex expression in HT29 colon cancer cells and its underlying mechanisms.

Methods: Effect of SDF-1 on E-cadherin/β-catenin expression was detected by immunocytochemistry. E-cadherin and β-catenin mRNA expression levels were measured by reverse transcriptase-polymerase chain reaction. SDF-1-induced phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT and β-catenin was detected by Western blotting.

Results: The E-cadherin and β-catenin mRNA expression levels in HT29 cells were lower 48 h after incubated with SDF-1 at the concentrations of 20 and 40 ng/mL (P<0.05). SDF-1-induced significant phosphorylation of PI3K/AKT and β-catenin. AMD3100 and LY294002 inhibited the phosphorylation of PI3K/AKT and β-catenin.

Conclusion: SDF-1 down-regulates the E-cadherin/β-catenin complex expression in HT29 cells by decreasing mRNA synthesis and increasing β-catenin phosphorylation.

Keywords: CXCR4; Colon cancer; E-cadherin; Phosphatidylinositol 3-kinase/AKT; Stromal cell-derived factor-1; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Chemokine CXCL12 / metabolism
  • Chemokine CXCL12 / pharmacology*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism*
  • Enzyme Inhibitors / metabolism
  • HT29 Cells / drug effects*
  • HT29 Cells / metabolism
  • Humans
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / metabolism
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • CXCR4 protein, human
  • Cadherins
  • Chemokine CXCL12
  • Enzyme Inhibitors
  • Phosphoinositide-3 Kinase Inhibitors
  • RNA, Messenger
  • Receptors, CXCR4
  • beta Catenin
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt