Tight junction protein 1 is regulated by transforming growth factor-β and contributes to cell motility in NSCLC cells

BMB Rep. 2015 Feb;48(2):115-20. doi: 10.5483/bmbrep.2015.48.2.035.

Abstract

Tight junction protein 1 (TJP1), a component of tight junction, has been reported to play a role in protein networks as an adaptor protein, and TJP1 expression is altered during tumor development. Here, we found that TJP1 expression was increased at the RNA and protein levels in TGF-β-stimulated lung cancer cells, A549. SB431542, a type-I TGF-β receptor inhibitor, as well as SB203580, a p38 kinase inhibitor, significantly abrogated the effect of TGF-β on TJP1 expression. Diphenyleneiodonium, an NADPH oxidase inhibitor, also attenuated TJP1 expression in response to TGF-β in lung cancer cells. When TJP1 expression was reduced by shRNA lentiviral particles in A549 cells (A549-sh TJP1), wound healing was much lower than in cells infected with control viral particles. Taken together, these data suggest that TGF-β enhances TJP1 expression, which may play a role beyond structural support in tight junctions during cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / pharmacology
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dioxoles / pharmacology
  • Gene Expression Regulation / drug effects*
  • Humans
  • Imidazoles / pharmacology
  • NADPH Oxidases / antagonists & inhibitors
  • NADPH Oxidases / metabolism
  • Onium Compounds / pharmacology
  • Pyridines / pharmacology
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Receptors, Transforming Growth Factor beta / antagonists & inhibitors
  • Receptors, Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology*
  • Zonula Occludens-1 Protein / antagonists & inhibitors
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • Benzamides
  • Dioxoles
  • Imidazoles
  • Onium Compounds
  • Pyridines
  • RNA, Small Interfering
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Zonula Occludens-1 Protein
  • diphenyleneiodonium
  • NADPH Oxidases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580