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

• Published in: International journal of cancer 2001-11, Vol.94 (3), p.328-334
• Main Authors: Hyuga, Sumiko, Kawasaki, Nana, Hyuga, Masashi, Ohta, Miyako, Shibayama, Rie, Kawanishi, Toru, Yamagata, Sadako, Yamagata, Tatsuya, Hayakawa, Takao
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Biological and medical sciences; Blotting, Western; c-Met protein; Cell Movement; c‐Met; Dissemination; DNA, Complementary - metabolism; Flow Cytometry; G(M1) Ganglioside - analogs & derivatives; G(M1) Ganglioside - pharmacology; ganglioside GD1^a; Gangliosides - metabolism; GD1a; Hepatocyte Growth Factor - metabolism; HGF; Medical sciences; Mice; motility; Neoplasms - metabolism; Phosphorylation; Precipitin Tests; Proto-Oncogene Proteins c-met - immunology; scattering; Signal Transduction; Stress Fibers - metabolism; Time Factors; Transfection; Tumor cell; Tumor Cells, Cultured; Tumors; tyrosine; Tyrosine - metabolism
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.1481

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. © 2001 Wiley‐Liss, Inc.