RRC ID 33962
Author Ohkawa Y, Momota H, Kato A, Hashimoto N, Tsuda Y, Kotani N, Honke K, Suzumura A, Furukawa K, Ohmi Y, Natsume A, Wakabayashi T, Furukawa K.
Title Ganglioside GD3 Enhances Invasiveness of Gliomas by Forming a Complex with Platelet-derived Growth Factor Receptor α and Yes Kinase.
Journal J Biol Chem
Abstract There have been a few studies on the ganglioside expression in human glioma tissues. However, the role of these gangliosides such as GD3 and GD2 has not been well understood. In this study we employed a genetically engineered mouse model of glioma to clarify the functions of GD3 in gliomas. Forced expression of platelet-derived growth factor B in cultured astrocytes derived from p53-deficient mice resulted in the expression of GD3 and GD2. GD3-positive astrocytes exhibited increased cell growth and invasion activities along with elevated phosphorylation of Akt and Yes kinase. By enzyme-mediated activation of radical sources reaction and mass spectrometry, we identified PDGF receptor α (PDGFRα) as a GD3-associated molecule. GD3-positive astrocytes showed a significant amount of PDGFRα in glycolipid-enriched microdomains/rafts compared with GD3-negative cells. Src kinase family Yes was co-precipitated with PDGFRα, and its pivotal role in the increased cell invasion of GD3-positive astrocytes was demonstrated by silencing with anti-Yes siRNA. Direct association between PDGFRα and GD3 was also shown, suggesting that GD3 forms ternary complex with PDGFRα and Yes. The fact that GD3, PDGFRα, and activated Yes were colocalized in lamellipodia and the edge of tumors in cultured cells and glioma tissues, respectively, suggests that GD3 induced by platelet-derived growth factor B enhances PDGF signals in glycolipid-enriched microdomain/rafts, leading to the promotion of malignant phenotypes such as cell proliferation and invasion in gliomas.
Volume 290(26)
Pages 16043-58
Published 2015-6-26
DOI 10.1074/jbc.M114.635755
PII S0021-9258(20)58436-6
PMID 25940087
PMC PMC4481208
MeSH Animals Brain Neoplasms / enzymology Brain Neoplasms / genetics Brain Neoplasms / metabolism* Gangliosides / metabolism* Glioma / enzymology Glioma / genetics Glioma / metabolism* Humans Mice Neoplasm Invasiveness Protein Binding Proto-Oncogene Proteins c-yes / genetics Proto-Oncogene Proteins c-yes / metabolism* Receptor, Platelet-Derived Growth Factor alpha / genetics Receptor, Platelet-Derived Growth Factor alpha / metabolism*
IF 4.238
Times Cited 33
Mice RBRC01361