Ganglioside GD1a negatively regulates hepatocyte growth factor expression through caveolin-1 at the transcriptional level in murine osteosarcoma cells

Lan Zhang, Yinan Wang, Li Wang, Ting Cao, Sumiko Hyuga, Toshinori Sato, Yingliang Wu, Sadako Yamagata, Tatsuya Yamagata

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Hepatocyte growth factor (HGF) is a mesenchyme-derived, multifunctional protein that is implicated in tumor growth and invasive behavior. Some tumor cells express both HGF and its receptor MET, forming an autocrine loop that permanently activates it. Ganglioside GD1a suppresses metastatic capacity in murine FBJ osteosarcoma cells and MET phosphorylation activated by HGF binding, but the signaling pathway controlling HGF production has not been fully explored. Methods: Expression of HGF, caveolins, or MET of the cells that had been transfected with siRNA or cDNA directed to GM2/GD2 synthase, caveolin-1 or HGF was determined by semi-quantitative RT-PCR and Western blots. Results: HGF expression in highly metastatic, GD1a-deficient FBJ-LL cells was higher than that in the poorly metastatic, GD1a-rich FBJ-S1 cells. Transfection with GM2/GD2 synthase cDNA increased GD1a levels in FBJ-LL cells and suppressed HGF expression. Treatment with siRNAs directed toward GM2/GD2 synthase in FBJ-S1 cells reduced gangliosides and augmented HGF expression. GD1a was found to be the only ganglioside species suppressing HGF expression upon addition to FBJ-LL cells. HGF expression was decreased by GD1a addition to FBJ-LL cells after 48 h, enough to induce caveolin-1 expression. Silencing caveolin-1 up-regulated HGF, and the re-introduction of caveolin-1 cDNA decreased HGF expression. Caveolin-1 suppressed MET phosphorylation. We also found GD1a regulation of HGF in Lewis lung carcinoma cells. Conclusions: HGF expression was negatively regulated by GD1a through caveolin-1 at the transcriptional level via the suppression of MET phosphorylation. General significance: This is the first report that ganglioside GD1a negatively regulates HGF expression through caveolin-1.

Original languageEnglish
Pages (from-to)759-768
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1810
Issue number8
DOIs
Publication statusPublished - 2011 Aug 1

    Fingerprint

Keywords

  • Caveolin-1
  • FBJ cells
  • Ganglioside GD1a
  • Hepatocyte growth factor
  • MET
  • Metastasis
  • Osteosarcoma

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this