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Ganglioside GD1a regulation of caveolin-1 and Stim1 expression in mouse FBJ cells:Augmented expression of caveolin-1 and Stim1 in cells with increased GD1a content

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Abstract

GD1a was previously shown responsible for regulating cell motility, cellular adhesiveness to vitronectin, phosphorylation of c-Met and metastatic ability of mouse FBJ osteosarcoma cells. To determine the particular molecules regulated by GD1a, FBJ cells were assessed for tumor-related gene expression by semi-quantitative RT-PCR. Caveolin-1 and stromal interaction molecule 1 (Stim1) expression in FBJ-S1 cells, rich in GD1a, were found to be 6 and 4 times as much, respectively, than in FBJ-LL cells devoid of GD1a. Enhanced production of caveolin-1 in protein was confirmed by Western blotting. A low-metastatic FBJ-LL cell variant, having high GD1a expression through β1-4GalNAcT-1 (GM2/GD2 synthase) cDNA transfection (Hyuga S, et al, Int J Cancer 83: 685-91, 1999), showed enhanced production of caveolin-1 and Stim1 in mRNA and protein, compared to mock-transfectant M5. Incubation of FBJ-M5 cells with exogenous GD1a augmented the expression of caveolin-1 in mRNA and protein and Stim1 in mRNA as well. Treatment of FBJ-S1 with fumonisin B1, an inhibitor of N-acylsphinganine synthesis, for 15 days caused the complete depletion of gangliosides and suppressed the expression of caveolin-1 and Stim1. St3gal5 siRNA transfected cells showed decreased expression of caveolin-1 and Stim1 mRNA, as well as St3gal5 mRNA. These findings clearly indicate ganglioside GD1a to be involved in the regulation of the transformation suppressor genes, caveolin-1 and Stim1. Moreover, treatment with GD1a of mouse melanoma B16 cells and human hepatoma HepG2 cells brought about elevated expression of caveolin-1 and Stim1.

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Abbreviations

GD1a:

Neu5Acα3Galβ3GalNAcβ4(Neu5Acα3)Galβ4GlcCer

GD3:

Neu5Acα8Neu5Acα3Galβ4GlcCer

Gg3:

GalNAcβ4Galβ4 Glc

GM1:

Galβ3GalNAcβ4(Neu5Acα3)Galβ4GlcCer

GM1b:

Neu5Acα3Galβ3GalNAcβ4Galβ4GlcCer

GM3:

Neu5Acα3Galβ4GlcCer

GT1b:

Neu5Acα3Galβ3GalNAcβ4(Neu-5Acα8Neu5Acα3)Galβ4GlcCer

GM2/GD2 synthase:

UDP-N-acetyl-α-D-galactosamine: (N-acetylneuraminyl)-galactosylglucosylceramide-β-1,4-N-acetylgalactosaminyltransferase

HPTLC:

high performance thin layer chromatography

PCR:

polymerase chain reaction

D-PDMP:

D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol

St3gal5:

CMP-NeuAc:lactosylceramide alpha-2,3-sialyltransferase

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Authors and Affiliations

  1. Laboratory of Tumor Biology and Glycobiology, Shenyang Pharmaceutical University, Shenyang, 110016, People’s Republic of China

    Li Wang, Pu Wang, Dan Hu, Sadako Yamagata & Tatsuya Yamagata

  2. Department of Neurology, Dokkyo University School of Medicine, Shimotsuga, Tochigi, 321-0293, Japan

    Shizuka Takaku

  3. Department of Clinical Research, Oriental Medicine Research Center, The Kitasato Institute, Minato-ku, Tokyo, 108-8642, Japan

    Sumiko Hyuga

  4. Department of Biosciences and Informatics, Keio University, Hiyoshi, Yokohama, 223-8522, Japan

    Toshinori Sato

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  1. Li Wang
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  2. Shizuka Takaku
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  3. Pu Wang
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Correspondence to Tatsuya Yamagata.

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Li Wang and Shizuka Takaku are equal contributors to the present work

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Wang, L., Takaku, S., Wang, P. et al. Ganglioside GD1a regulation of caveolin-1 and Stim1 expression in mouse FBJ cells:Augmented expression of caveolin-1 and Stim1 in cells with increased GD1a content. Glycoconj J 23, 303–315 (2006). https://doi.org/10.1007/s10719-006-5742-3

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