Ganglioside GD1a inhibits HGF-induced motility and scattering of cancer cells through suppression of tyrosine phosphorylation of c-Met.

Abstract

We previously reported that ganglioside GD1a, which is highly expressed in poorly metastatic FBJ-S1 cells, inhibits the serum-induced motility of FBJ-LL cells and that the metastatic potential of FBJ-LL cells is completely suppressed by enforced GD1a expression (Hyuga et al., Int J Cancer 1999;83:685-91). We recently discovered that hepatocyte growth factor (HGF) induces FBJ-LL cell motility. In the present study, the HGF-induced motility of FBJ-S1 cells was found to be one-thirtieth that of FBJ-LL cells. This motility of GD1a-expressing transfectants, which were produced by transfection of FBJ-LL cells with GM2/GD2 synthase cDNA, decreased with increases in their GD1a expression and HGF induced almost no motility in GD1a-pretreated FBJ-LL cells, indicating that GD1a inhibits the HGF-induced motility of FBJ-LL cells. The expression of the HGF receptor c-Met on FBJ-S1 cells, FBJ-LL cells, transfectants and a mock-transfectant was almost the same. The level of tyrosine phosphorylation of c-Met after HGF stimulation in FBJ-S1 cells, GD1a-pretreated FBJ-LL cells and a GD1a-expressing transfectant was significantly lower than in FBJ-LL cells and a mock-transfectant. These findings suggested that GD1a inhibits the HGF-induced motility of FBJ-LL cells through suppression of tyrosine phosphorylation of c-Met. HepG2 cells, a human hepatoma cell line, were used to investigate whether GD1a interferes with other cancer cells expressing c-Met. HepG2 cells did not express GD1a. HGF induced cell scattering of HepG2 cells and the scattering was inhibited by pretreating the cells with GD1a. The c-Met in the cells was autophosphorylated by stimulation with HGF, but after treating the cells with GD1a, the HGF-induced autophosphorylation of c-Met was suppressed. These results suggest that GD1a acts as a negative regulator of c-Met in cancer cells.

• Authors: S Hyuga, N Kawasaki, M Hyuga, M Ohta, R Shibayama, T Kawanishi, S Yamagata, T Yamagata, T Hayakawa
• Journal: International journal of cancer (Int J Cancer) Vol. 94 Issue 3 Pg. 328-34 (Nov 01 2001) ISSN: 0020-7136 [Print] United States
• PMID: 11745410 (Publication Type: Journal Article)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• Actins
• DNA, Complementary
• Gangliosides
• ganglioside GD1alpha
• G(M1) Ganglioside
• Tyrosine
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met

Topics

• Actins (metabolism)
• Animals
• Blotting, Western
• Cell Movement
• DNA, Complementary (metabolism)
• Flow Cytometry
• G(M1) Ganglioside (analogs & derivatives, pharmacology)
• Gangliosides (metabolism)
• Hepatocyte Growth Factor (metabolism)
• Mice
• Neoplasms (metabolism)
• Phosphorylation
• Precipitin Tests
• Proto-Oncogene Proteins c-met (immunology)
• Signal Transduction
• Stress Fibers (metabolism)
• Time Factors
• Transfection
• Tumor Cells, Cultured
• Tyrosine (metabolism)