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Ganglioside GM3 promotes cell migration by regulating MAPK and c-Fos/AP-1

Oncogene volume 25, pages 3948–3955 (2006)Cite this article

Abstract

Gangliosides have been proposed as modulators of transmembrane signaling. Recently, GM3, a glycosphingolipid containing monosaialic acids, is thought to be one of the key molecules of signal transduction in mammalian cells. In this study, we used mouse embryonic fibroblast cell lines (MEFs) established from sialyltransferase-I knockout mice (GM3 synthase KO mice) to evaluate the regulation of mitogenic signals by gangliosides. Cell proliferation assay revealed a higher growth potential of GM3 KO MEFs. Immunoblots showed upregulation of Ras/Raf/MEK/ERK pathway in GM3 KO MEFs, and these signals resulted in enhanced translocation of ERK into the nuclei. Further, both exogenous and endogenous add-back of GM3 decreased the activities of MAPK in GM3 KO MEFs. In addition, GM3 KO MEFs formed foci in high-density culture condition, and analyses of cell cycle modulators revealed the resistance of GM3 KO MEFs for entering cell cycle arrest. Finally, sustained expressions of c-Fos in GM3 KO MEFs were shown to correlate with DNA-binding activity between c-Fos and AP-1. These results demonstrate that the deletion of sialyltransferase-I changes the character of MEFs to a highly activated state of the MAPK pathway, indicating the critical role of GM3 as a regulator of membrane-transmitted signals.

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References

  • Ballif BA, Blenis J . (2001). Cell Growth Differ 12: 397–408.

  • Blagosklonny MV . (1999). BioEssays 21: 704–709.

  • Cobb MH, Goldsmith EJ . (1995). J Biol Chem 270: 14843–14846.

  • Cullen PJ . (2001). Curr Biol 11: 342–344.

  • Danen EH, Yamada KM . (2001). J Cell Physiol 189: 1–13.

  • Deng C, Zhang P, Harper JW, Elledge SJ, Leder P . (1995). Cell 82: 675–684.

  • Dignam JD, Lebovitz RM, Roeder RG . (1983). Nucleic Acids Res 11: 1475–1489.

  • Fu M, Wang C, Li Z, Sakamaki T, Pestell RG . (2004). Endocrinology 145: 5439–5447.

  • Galbiati F, Volonte D, Engelman JA, Watanabe G, Burk R, Pestell RG et al. (1998). EMBO J 17: 6633–6648.

  • Garofalo T, Sorice M, Misasi R, Cinque B, Mattei V, Pontieri GM et al. (2002). J Lipid Res 43: 971–978.

  • Gorbacheva VY, Lindner D, Sen GC, Vestal DJ . (2002). J Biol Chem 277: 6080–6087.

  • Gouni-Berthold I, Seul C, Ko Y, Hescheler J, Sachinidis A . (2001). Hypertension 38: 1030–1037.

  • Groth A, Willumsen BM . (2005). Cell Signal 17: 1063–1073.

  • Gum R, Wang H, Lengyel E, Juarez J, Boyd D . (1997). Oncogene 14: 1481–1493.

  • Hakomori S, Yamamura S, Handa AK . (1998). Ann NY Acad Sci 845: 1–10.

  • Hanai N, Nores GA, MacLeod C, Torres-Mendez CR, Hakomori S . (1998). J Biol Chem 263: 10915–10921.

  • Hashiramoto A, Sano H, Maekawa T, Kawahito Y, Kimura S, Kusaka Y et al. (1999). Arthritis Rheum 42: 954–962.

  • Hoffmann E, Thiefes A, Buhrow D, Dittrich-Breoholz O, Schneider H, Resch K et al. (2005). J Biol Chem 280: 9706–9718.

  • Huwiler A, Kolter T, Pfeilschifter J, Sandhoff K . (2000). Biochim Biophys Acta 1485: 63–99.

  • Itano N, Atsumi F, Sawai T, Yamada Y, Miyaishi O, Senga T et al. (2002). Proc Natl Acad Sci USA 99: 3609–3614.

  • Iwabuchi K, Yamamura S, Prinetti A, Handa K, Hakomori S . (1998). J Biol Chem 273: 9130–9138.

  • Kawahito Y, Kondo M, Tsubouchi Y, Hashiramoto A, Bishop-Bailey D, Inoue K et al. (2000). J Clin Invest 106: 189–197.

  • Kolch W . (2000). Biochem J 351: 289–305.

  • Kono M, Takashima S, Liu H, Inoue M, Kojima N, Lee YC et al. (1998). Biochem Biophys Res Commun 253: 170–175.

  • Li A, Blow JJ . (2001). Nat Cell Biol 3: 182–184.

  • Li R, Liu Y, Ladisch S . (2001). J Biol Chem 276: 42782–42792.

  • Li R, Manela J, Kong Y, Ladisch S . (2000). J Biol Chem 275: 34213–34223.

  • Matyas GR, Aaronson SA, Brady RO, Fishman PH . (1987). Proc Natl Acad Sci USA 84: 6065–6068.

  • Monje P, Marinnisen M, Gutkind JS . (2003). Mol Cell Biol 23: 7030–7043.

  • Murphy LO, Smith S, Chen P, Finger DC, Blenis J . (2002). Nat Cell Biol 4: 556–564.

  • Nakatsuji Y, Miller RH . (2001). J Neurosci Res 66: 487–496.

  • Noll EN, Lin J, Nakatsuji Y, Miller RH, Black PM . (2001). Exp Neurol 168: 300–309.

  • Paller AS, Arnsmeier SL, Alvarez-Franco M, Bremer EG . (1993). Invest Dermatol 100: 841–845.

  • Radeff-Huang J, Seasholtz TM, Matteo RG, Brown JH . (2004). Cell Biochem 9: 949–966.

  • Scorrano L, Petronilli V, Colonna R, Di Lisa F, Bernardi P . (1999). J Biol Chem 274: 24657–24663.

  • Smart EJ, Graf GA, McNiven MA, Sessa WC, Engelman JA, Scherer PE et al. (1999). Mol Cell Biol 19: 7289–7304.

  • Suarez Pestana E, Tenev T, Gross S, Stoyanov B, Ogata M, Bohmer FD . (1999). Oncogene 18: 4069–4079.

  • Tanaka T, Yoshida N, Kishimoto T, Akira S . (1997). EMBO J 16: 7432–7443.

  • Van Brocklyn J, Bremer EG, Yates AJ . (1993). J Neurochem 61: 371–374.

  • van Meer G, Holthuis JC . (2000). Biochim Biophys Acta 26: 145–170.

  • Wang XQ, Sun P, O'Gorman M, Tai T, Paller AS . (2001). Gycobiology 11: 515–522.

  • Wang XQ, Sun P, Paller AS . (2003). J Biol Chem 278: 48770–48778.

  • Yamashita T, Hashiramoto A, Haluzik M, Mizukami H, Beck S, Norton A et al. (2003). Proc Natl Acad Sci USA 100: 3445–3449.

  • Zou Y, Hu Y, Metzler B, Xu Q . (1998). Int J Mol Med 1: 827–834.

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Acknowledgements

Special thanks goes to Dr Richard L Proia for his kind support throughout this work.

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Authors and Affiliations

  1. Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    A Hashiramoto, H Mizukami & T Yamashita

  2. Depertment of Rheumatology, Kobe University FHS School of Medicine, Kobe, Japan

    A Hashiramoto

  3. Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan

    H Mizukami

  4. Department of Cell Processing, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    T Yamashita

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  1. A Hashiramoto
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Correspondence to A Hashiramoto.

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Hashiramoto, A., Mizukami, H. & Yamashita, T. Ganglioside GM3 promotes cell migration by regulating MAPK and c-Fos/AP-1. Oncogene 25, 3948–3955 (2006). https://doi.org/10.1038/sj.onc.1209416

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