LRG1 modulates invasion and migration of glioma cell lines through TGF-β signaling pathway

Acta Histochem. 2015 Jul;117(6):551-8. doi: 10.1016/j.acthis.2015.05.001. Epub 2015 Jun 3.

Abstract

Studies have shown that the abnormal expression of leucine-rich α2 glycoprotein 1 (LRG1) is associated with multiple malignancies, yet its role in glioma pathology remains to be elucidated. In this study, we investigated the role of LRG1 in regulating proliferation, migration and invasion of glioma cells by establishing glioma cell strains with constitutively silenced or elevated LRG1 expression. LRG1 overexpression and silenced cell lines demonstrated modulation of glioma cellular proliferation, migration and invasion through MTT, cell scratching and Transwell assays. Furthermore, overexpression of LRG1 led to augmented activation of transforming growth factor-β (TGF-β) signaling pathway as well as downregulation of E-cadherin and resultant enhanced invasiveness, which was reversed by TGF-β signaling pathway inhibitor SB431542. In summary, our findings suggest that LRG1 promotes invasion and migration of glioma cells through TGF-β signaling pathway.

Keywords: Glioma; Invasion; LRG1; Migration; TGF-β signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / pharmacology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Dioxoles / pharmacology
  • Glioma / metabolism*
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Neoplasm Invasiveness
  • Receptors, Transforming Growth Factor beta / antagonists & inhibitors
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / metabolism*

Substances

  • 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • Benzamides
  • Dioxoles
  • Glycoproteins
  • LRG1 protein, human
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta