title: Ganglioside GM3 promotes HGF-stimulated motility of murine hepatoma cell through enhanced phosphorylation of cMet at specific tyrosine sites and PI3K/Akt-mediated migration signaling.
abstract: Ganglioside GM3 plays a well-documented and important role in the regulation of tumor cell proliferation, invasion, and metastasis by modulating tyrosine kinase growth factor receptors. However, the effect of GM3 on the hepatocyte growth factor receptor (HGFR, cMet) has not been fully delineated. In the current study, we investigated how GM3 affects cMet signaling and HGF-stimulated cell motility and migration using three hepatic cancer cell lines of mouse (Hca/A2, Hca/16A3, and Hepa1-6). Decreasing GM3 expression with the use of P4, a specific inhibitor for ganglioside synthesis inhibited the HGF-stimulated phosphorylation of cMet and activity of PI3K/Akt signaling pathway. In contrast, the increased expression of GM3 as a result of adding exogenous GM3 enhanced the HGF-stimulated phosphorylation of cMet and activity of PI3K/Akt signaling pathway. Furthermore, HGF-stimulated cell motility and migration in vitro were inhibited by reduced expression of GM3 and enhanced by increased expression of GM3. All the observations indicate that ganglioside GM3 promotes HGF-stimulated motility of murine hepatoma cell through enhanced phosphorylation of cMet at specific tyrosine sites and PI3K/Akt-mediated migration signaling.
authors.affiliation: Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Huang
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhong
authors.forename: Jianing
authors.initials: J
authors.lastname: Zhang
authors.forename: Keli
authors.initials: K
authors.lastname: Ma
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005678:G(M2) Ganglioside / Q000494:pharmacology; D005679:G(M3) Ganglioside / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005679:G(M3) Ganglioside; D005678:G(M2) Ganglioside; D019000:Phosphotyrosine; D017228:Hepatocyte Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt