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GM3 and cancer

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Abstract

Our studies during the early 1970s showed that expression of GM3, the simplest ganglioside and an abundant animal cell membrane component, is reduced during malignant transformation of cells by oncogenic viruses. Levels of mRNA for GM3 synthase were reduced in avian and mammalian cells transformed by oncoprotein “v-Jun”, and overexpression of GM3 synthase in the transformed cells caused reversion from transformed to normal cell-like phenotype. GM3 has a well-documented inhibitory effect on activation of growth factor receptors (GFRs), particularly epidermal GFR (EGFR). De-N-acetyl GM3, which is expressed in some invasive human cancer cells, has an enhancing effect on EGFR activation. The important role of the sialosyl group of GM3 was demonstrated using NEU3, a plasma membrane-associated sialidase that selectively remove sialic acids from gangliosides GM3 and GD1a and is up-regulated in many human cancer cells. GM3 is highly enriched in a type of membrane microdomain termed “glycosynapse”, and forms complexes with co-localized cell signaling molecules, including Src family kinases, certain tetraspanins (e.g., CD9, CD81, CD82), integrins, and GFRs (e.g., fibroblast growth factor receptor and hepatocyte growth factor receptor c-Met). Studies by our group and others indicate that GM3 modulates cell adhesion, growth, and motility by altering molecular organization in glycosynaptic microdomains and the activation levels of co-localized signaling molecules that are involved in cancer pathogenesis.

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Abbreviations

GFR:

Growth factor receptor

EGFR:

Epidermal growth factor receptor

GSL:

Glycosphingolipid

TS:

Tetraspanin

GPI:

Glycosylphosphatidylinositol

GEM:

Glycolipid-enriched microdomain

References

  1. Hakomori, S.: Traveling for the glycosphingolipid path. Glycoconj. J. 17(7–9), 627–647 (2000)

    Article  CAS  PubMed  Google Scholar 

  2. Hakomori, S.I.: Structure and function of glycosphingolipids and sphingolipids: recollections and future trends. Biochim. Biophys. Acta 1780(3), 325–346 (2008). doi:10.1016/j.bbagen.2007.08.015

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Hakomori, S.I., Murakami, W.T.: Glycolipids of hamster fibroblasts and derived malignant-transformed cell lines. Proc. Natl. Acad. Sci. U. S. A. 59(1), 254–261 (1968)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Mora, P.T., Brady, R.O., Bradley, R.M., McFarland, V.W.: Gangliosides in DNA virus-transformed and spontaneously transformed tumorigenic mouse cell lines. Proc. Natl. Acad. Sci. U. S. A. 63(4), 1290–1296 (1969)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Hakomori, S.I., Saito, T., Vogt, P.K.: Transformation by rous sarcoma virus: effects on cellular glycolipids. Virology 44(3), 609–621 (1971)

    Article  CAS  PubMed  Google Scholar 

  6. Hakomori, S.I., Wyke, J.A., Vogt, P.K.: Glycolipids of chick embryo fibroblasts infected with temperature-sensitive mutants of avian sarcoma viruses. Virology 76(2), 485–493 (1977)

    Article  CAS  PubMed  Google Scholar 

  7. Vogt, P.K.: Jun, the oncoprotein. Oncogene 20(19), 2365–2377 (2001). doi:10.1038/sj.onc.1204443

    Article  CAS  PubMed  Google Scholar 

  8. Miura, Y., Kainuma, M., Jiang, H., Velasco, H., Vogt, P.K., Hakomori, S.: Reversion of the Jun-induced oncogenic phenotype by enhanced synthesis of sialosyllactosylceramide (GM3 ganglioside). Proc. Natl. Acad. Sci. U. S. A. 101(46), 16204–16209 (2004). doi:10.1073/pnas.0407297101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Ono, M., Handa, K., Sonnino, S., Withers, D.A., Nagai, H., Hakomori, S.: GM3 ganglioside inhibits CD9-facilitated haptotactic cell motility: coexpression of GM3 and CD9 is essential in the downregulation of tumor cell motility and malignancy. Biochemistry 40(21), 6414–6421 (2001)

    Article  CAS  PubMed  Google Scholar 

  10. Abercrombie, M., Ambrose, E.J.: The surface properties of cancer cells: a review. Cancer Res. 22, 525–548 (1962)

    CAS  PubMed  Google Scholar 

  11. Abercrombie, M., Heaysman, J.E.: Observations on the social behaviour of cells in tissue culture. II. Monolayering of fibroblasts. Exp. Cell Res. 6(2), 293–306 (1954)

    Article  CAS  PubMed  Google Scholar 

  12. Hakomori, S.: Cell density-dependent changes of glycolipid concentrations in fibroblasts, and loss of this response in virus-transformed cells. Proc. Natl. Acad. Sci. U. S. A. 67(4), 1741–1747 (1970)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Robbins, P.W., Macpherson, I.: Control of glycolipid synthesis in a cultured hamster cell line. Nature 229(5286), 569–570 (1971)

    Article  CAS  PubMed  Google Scholar 

  14. Sakiyama, H., Gross, S.K., Robbins, P.W.: Glycolipid synthesis in normal and virus-transformed hamster cell lines. Proc. Natl. Acad. Sci. U. S. A. 69(4), 872–876 (1972)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Lingwood, C.A., Hakomori, S.: Selective inhibition of cell growth and associated changes in glycolipid metabolism induced by monovalent antibodies to glycolipids. Exp. Cell Res. 108(2), 385–391 (1977)

    Article  CAS  PubMed  Google Scholar 

  16. Bremer, E.G., Hakomori, S.: GM3 ganglioside induces hamster fibroblast growth inhibition in chemically-defined medium: ganglioside may regulate growth factor receptor function. Biochem. Biophys. Res. Commun. 106(3), 711–718 (1982)

    Article  CAS  PubMed  Google Scholar 

  17. Bremer, E.G., Schlessinger, J., Hakomori, S.: Ganglioside-mediated modulation of cell growth. Specific effects of GM3 on tyrosine phosphorylation of the epidermal growth factor receptor. J. Biol. Chem. 261(5), 2434–2440 (1986)

    CAS  PubMed  Google Scholar 

  18. Weis, F.M., Davis, R.J.: Regulation of epidermal growth factor receptor signal transduction. Role of gangliosides. J. Biol. Chem. 265(20), 12059–12066 (1990)

    CAS  PubMed  Google Scholar 

  19. Miljan, E.A., Meuillet, E.J., Mania-Farnell, B., George, D., Yamamoto, H., Simon, H.G., Bremer, E.G.: Interaction of the extracellular domain of the epidermal growth factor receptor with gangliosides. J. Biol. Chem. 277(12), 10108–10113 (2002). doi:10.1074/jbc.M111669200

    Article  CAS  PubMed  Google Scholar 

  20. Hanai, N., Dohi, T., Nores, G.A., Hakomori, S.: A novel ganglioside, de-N-acetyl-GM3 (II3NeuNH2LacCer), acting as a strong promoter for epidermal growth factor receptor kinase and as a stimulator for cell growth. J. Biol. Chem. 263(13), 6296–6301 (1988)

    CAS  PubMed  Google Scholar 

  21. Hanai, N., Nores, G., Torres-Mendez, C.R., Hakomori, S.: Modified ganglioside as a possible modulator of transmembrane signaling mechanism through growth factor receptors: a preliminary note. Biochem. Biophys. Res. Commun. 147(1), 127–134 (1987)

    Article  CAS  PubMed  Google Scholar 

  22. Hanai, N., Nores, G.A., MacLeod, C., Torres-Mendez, C.R., Hakomori, S.: Ganglioside-mediated modulation of cell growth. Specific effects of GM3 and lyso-GM3 in tyrosine phosphorylation of the epidermal growth factor receptor. J. Biol. Chem. 263(22), 10915–10921 (1988)

    CAS  PubMed  Google Scholar 

  23. Kawashima, N., Qu, H., Lobaton, M., Zhu, Z., Sollogoub, M., Cavenee, W.K., Handa, K., Hakomori, S.I., Zhang, Y.: Efficient synthesis of chloro-derivatives of sialosyllactosylceramide, and their enhanced inhibitory effect on epidermal growth factor receptor activation. Oncol. Lett. 7(4), 933–940 (2014). doi:10.3892/ol.2014.1887

    PubMed Central  CAS  PubMed  Google Scholar 

  24. Nores, G.A., Hanai, N., Levery, S.B., Eaton, H.L., Salyan, E.K., Hakomori, S.: Synthesis and characterization of lyso-GM3 (II3Neu5Ac Lactosyl sphingosine), de-N-acetyl-GM3 (II3NeuNH2 lactosyl Cer), and related compounds. Carbohydr. Res. 179, 393–410 (1988)

    Article  CAS  PubMed  Google Scholar 

  25. Nores, G.A., Hanai, N., Levery, S.B., Eaton, H.L., Salyan, M.E., Hakomori, S.: Synthesis and characterization of ganglioside GM3 derivatives: lyso-GM3, de-N-acetyl-GM3, and other compounds. Methods Enzymol. 179, 242–253 (1989)

    Article  CAS  PubMed  Google Scholar 

  26. Dohi, T., Nores, G., Hakomori, S.: An IgG3 monoclonal antibody established after immunization with GM3 lactone: immunochemical specificity and inhibition of melanoma cell growth in vitro and in vivo. Cancer Res. 48(20), 5680–5685 (1988)

    CAS  PubMed  Google Scholar 

  27. Zhou, Q., Hakomori, S., Kitamura, K., Igarashi, Y.: GM3 directly inhibits tyrosine phosphorylation and de-N-acetyl-GM3 directly enhances serine phosphorylation of epidermal growth factor receptor, independently of receptor-receptor interaction. J. Biol. Chem. 269(3), 1959–1965 (1994)

    CAS  PubMed  Google Scholar 

  28. Liu, J.W., Sun, P., Yan, Q., Paller, A.S., Gerami, P., Ho, N., Vashi, N., Le Poole, I.C., Wang, X.Q.: De-N-acetyl GM3 promotes melanoma cell migration and invasion through urokinase plasminogen activator receptor signaling-dependent MMP-2 activation. Cancer Res. 69(22), 8662–8669 (2009). doi:10.1158/0008-5472.CAN-09-1099

    Article  CAS  PubMed  Google Scholar 

  29. Hakomori, S.I.: Glycosynaptic microdomains controlling tumor cell phenotype through alteration of cell growth, adhesion, and motility. FEBS Lett. 584(9), 1901–1906 (2010). doi:10.1016/j.febslet.2009.10.065

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Meuillet, E.J., Kroes, R., Yamamoto, H., Warner, T.G., Ferrari, J., Mania-Farnell, B., George, D., Rebbaa, A., Moskal, J.R., Bremer, E.G.: Sialidase gene transfection enhances epidermal growth factor receptor activity in an epidermoid carcinoma cell line, A431. Cancer Res. 59(1), 234–240 (1999)

    CAS  PubMed  Google Scholar 

  31. Hasegawa, T., Yamaguchi, K., Wada, T., Takeda, A., Itoyama, Y., Miyagi, T.: Molecular cloning of mouse ganglioside sialidase and its increased expression in Neuro2a cell differentiation. J. Biol. Chem. 275(11), 8007–8015 (2000)

    Article  CAS  PubMed  Google Scholar 

  32. Papini, N., Anastasia, L., Tringali, C., Croci, G., Bresciani, R., Yamaguchi, K., Miyagi, T., Preti, A., Prinetti, A., Prioni, S., Sonnino, S., Tettamanti, G., Venerando, B., Monti, E.: The plasma membrane-associated sialidase MmNEU3 modifies the ganglioside pattern of adjacent cells supporting its involvement in cell-to-cell interactions. J. Biol. Chem. 279(17), 16989–16995 (2004). doi:10.1074/jbc.M400881200

    Article  CAS  PubMed  Google Scholar 

  33. Wada, T., Hata, K., Yamaguchi, K., Shiozaki, K., Koseki, K., Moriya, S., Miyagi, T.: A crucial role of plasma membrane-associated sialidase in the survival of human cancer cells. Oncogene 26(17), 2483–2490 (2007). doi:10.1038/sj.onc.1210341

    Article  CAS  PubMed  Google Scholar 

  34. Shiozaki, K., Yamaguchi, K., Sato, I., Miyagi, T.: Plasma membrane-associated sialidase (NEU3) promotes formation of colonic aberrant crypt foci in azoxymethane-treated transgenic mice. Cancer Sci. 100(4), 588–594 (2009). doi:10.1111/j.1349-7006.2008.01080.x

    Article  CAS  PubMed  Google Scholar 

  35. Tringali, C., Lupo, B., Silvestri, I., Papini, N., Anastasia, L., Tettamanti, G., Venerando, B.: The plasma membrane sialidase NEU3 regulates the malignancy of renal carcinoma cells by controlling beta1 integrin internalization and recycling. J. Biol. Chem. 287(51), 42835–42845 (2012). doi:10.1074/jbc.M112.407718

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Ueno, S., Saito, S., Wada, T., Yamaguchi, K., Satoh, M., Arai, Y., Miyagi, T.: Plasma membrane-associated sialidase is up-regulated in renal cell carcinoma and promotes interleukin-6-induced apoptosis suppression and cell motility. J. Biol. Chem. 281(12), 7756–7764 (2006). doi:10.1074/jbc.M509668200

    Article  CAS  PubMed  Google Scholar 

  37. Miyata, M., Kambe, M., Tajima, O., Moriya, S., Sawaki, H., Hotta, H., Kondo, Y., Narimatsu, H., Miyagi, T., Furukawa, K., Furukawa, K.: Membrane sialidase NEU3 is highly expressed in human melanoma cells promoting cell growth with minimal changes in the composition of gangliosides. Cancer Sci. 102(12), 2139–2149 (2011). doi:10.1111/j.1349-7006.2011.02086.x

    Article  CAS  PubMed  Google Scholar 

  38. Bonardi, D., Papini, N., Pasini, M., Dileo, L., Orizio, F., Monti, E., Caimi, L., Venerando, B., Bresciani, R.: Sialidase NEU3 dynamically associates to different membrane domains specifically modifying their ganglioside pattern and triggering Akt phosphorylation. PLoS One 9(6), e99405 (2014). doi:10.1371/journal.pone.0099405

    Article  PubMed Central  PubMed  Google Scholar 

  39. Banda, K., Gregg, C.J., Chow, R., Varki, N.M., Varki, A.: Metabolism of vertebrate amino sugars with N-glycolyl groups: mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid. J. Biol. Chem. 287(34), 28852–28864 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Tringali, C., Silvestri, I., Testa, F., Baldassari, P., Anastasia, L., Mortarini, R., Anichini, A., Lopez-Requena, A., Tettamanti, G., Venerando, B.: Molecular subtyping of metastatic melanoma based on cell ganglioside metabolism profiles. BMC Cancer 14(1), 560 (2014)

    Article  PubMed Central  PubMed  Google Scholar 

  41. Lahera, T., Calvo, A., Torres, G., Rengifo, C.E., Quintero, S., Arango Mdel, C., Danta, D., Vázquez, J.M., Escobar, X., Carr, A.: Prognostic Role of 14F7 Mab Immunoreactivity against N-Glycolyl GM3 Ganglioside in Colon Cancer. J. Oncol. 2014 (2014)

  42. Casadesus, A.V., Fernandez-Marrero, Y., Clavell, M., Hernandez, T., Lopez-Requena, A., Moreno, E., Gomez, J.A.: A shift from N-glycolyl- to N-acetyl-sialic acid in the GM3 ganglioside impairs tumor development in mouse lymphocytic leukemia cells. Glycoconj. J. Glycoconj. J. 30(7), 687–699 (2013)

    Article  CAS  Google Scholar 

  43. Tillack, T.W., Allietta, M., Moran, R.E., Young Jr., W.W.: Localization of globoside and Forssman glycolipids on erythrocyte membranes. Biochim. Biophys. Acta 733(1), 15–24 (1983)

    Article  CAS  PubMed  Google Scholar 

  44. Rock, P., Allietta, M., Young Jr., W.W., Thompson, T.E., Tillack, T.W.: Ganglioside GM1 and asialo-GM1 at low concentration are preferentially incorporated into the gel phase in two-component, two-phase phosphatidylcholine bilayers. Biochemistry 30(1), 19–25 (1991)

    Article  CAS  PubMed  Google Scholar 

  45. Carter, W.G., Hakomori, S.: A new cell surface, detergent-insoluble glycoprotein matrix of human and hamster fibroblasts. The role of disulfide bonds in stabilization of the matrix. J. Biol. Chem. 256(13), 6953–6960 (1981)

    CAS  PubMed  Google Scholar 

  46. Okada, Y., Mugnai, G., Bremer, E.G., Hakomori, S.: Glycosphingolipids in detergent-insoluble substrate attachment matrix (DISAM) prepared from substrate attachment material (SAM). Their possible role in regulating cell adhesion. Exp. Cell Res. 155(2), 448–456 (1984)

    Article  CAS  PubMed  Google Scholar 

  47. Simons, K., van Meer, G.: Lipid sorting in epithelial cells. Biochemistry 27(17), 6197–6202 (1988)

    Article  CAS  PubMed  Google Scholar 

  48. Brown, D.A., London, E.: Structure of detergent-resistant membrane domains: does phase separation occur in biological membranes? Biochem. Biophys. Res. Commun. 240(1), 1–7 (1997). doi:10.1006/bbrc.1997.7575

    Article  CAS  PubMed  Google Scholar 

  49. Smart, E.J., Mineo, C., Anderson, R.G.: Clustered folate receptors deliver 5-methyltetrahydrofolate to cytoplasm of MA104 cells. J. Cell Biol. 134(5), 1169–1177 (1996)

    Article  CAS  PubMed  Google Scholar 

  50. Stefanova, I., Horejsi, V., Ansotegui, I.J., Knapp, W., Stockinger, H.: GPI-anchored cell-surface molecules complexed to protein tyrosine kinases. Science 254(5034), 1016–1019 (1991)

    Article  CAS  PubMed  Google Scholar 

  51. Kniep, B., Cinek, T., Angelisova, P., Horejsi, V.: Association of the GPI-anchored leucocyte surface glycoproteins with ganglioside GM3. Biochem. Biophys. Res. Commun. 203(2), 1069–1075 (1994)

    Article  CAS  PubMed  Google Scholar 

  52. Simons, K., Ikonen, E.: Functional rafts in cell membranes. Nature 387(6633), 569–572 (1997). doi:10.1038/42408

    Article  CAS  PubMed  Google Scholar 

  53. Handa, K., Hakomori, S.I.: Carbohydrate to carbohydrate interaction in development process and cancer progression. Glycoconj. J. 29(8–9), 627–637 (2012). doi:10.1007/s10719-012-9380-7

    Article  CAS  PubMed  Google Scholar 

  54. Kojima, N., Hakomori, S.: Specific interaction between gangliotriaosylceramide (Gg3) and sialosyllactosylceramide (GM3) as a basis for specific cellular recognition between lymphoma and melanoma cells. J. Biol. Chem. 264(34), 20159–20162 (1989)

    CAS  PubMed  Google Scholar 

  55. Kojima, N., Hakomori, S.: Cell adhesion, spreading, and motility of GM3-expressing cells based on glycolipid-glycolipid interaction. J. Biol. Chem. 266(26), 17552–17558 (1991)

    CAS  PubMed  Google Scholar 

  56. Yamamura, S., Handa, K., Hakomori, S.: A close association of GM3 with c-Src and Rho in GM3-enriched microdomains at the B16 melanoma cell surface membrane: a preliminary note. Biochem. Biophys. Res. Commun. 236(1), 218–222 (1997)

    Article  CAS  PubMed  Google Scholar 

  57. Iwabuchi, K., Handa, K., Hakomori, S.: Separation of “glycosphingolipid signaling domain” from caveolin-containing membrane fraction in mouse melanoma B16 cells and its role in cell adhesion coupled with signaling. J. Biol. Chem. 273(50), 33766–33773 (1998)

    Article  CAS  PubMed  Google Scholar 

  58. Prinetti, A., Iwabuchi, K., Hakomori, S.: Glycosphingolipid-enriched signaling domain in mouse neuroblastoma Neuro2a cells. Mechanism of ganglioside-dependent neuritogenesis. J. Biol. Chem. 274(30), 20916–20924 (1999)

    Article  CAS  PubMed  Google Scholar 

  59. Bromley, S.K., Burack, W.R., Johnson, K.G., Somersalo, K., Sims, T.N., Sumen, C., Davis, M.M., Shaw, A.S., Allen, P.M., Dustin, M.L.: The immunological synapse. Annu. Rev. Immunol. 19, 375–396 (2001). doi:10.1146/annurev.immunol.19.1.375

    Article  CAS  PubMed  Google Scholar 

  60. Viola, A., Schroeder, S., Sakakibara, Y., Lanzavecchia, A.: T lymphocyte costimulation mediated by reorganization of membrane microdomains. Science 283(5402), 680–682 (1999)

    Article  CAS  PubMed  Google Scholar 

  61. Hakomori, S.: Glycosylation defining cancer malignancy: new wine in an old bottle. Proc. Natl. Acad. Sci. U. S. A. 99(16), 10231–10233 (2002). doi:10.1073/pnas.172380699

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Ono, M., Handa, K., Withers, D.A., Hakomori, S.: Motility inhibition and apoptosis are induced by metastasis-suppressing gene product CD82 and its analogue CD9, with concurrent glycosylation. Cancer Res. 59(10), 2335–2339 (1999)

    CAS  PubMed  Google Scholar 

  63. Ono, M., Handa, K., Withers, D.A., Hakomori, S.: Glycosylation effect on membrane domain (GEM) involved in cell adhesion and motility: a preliminary note on functional alpha3, alpha5-CD82 glycosylation complex in ldlD 14 cells. Biochem. Biophys. Res. Commun. 279(3), 744–750 (2000). doi:10.1006/bbrc.2000.4030

    Article  CAS  PubMed  Google Scholar 

  64. Folch, J., Lees, M.: Proteolipides, a new type of tissue lipoproteins; their isolation from brain. J. Biol. Chem. 191(2), 807–817 (1951)

    CAS  PubMed  Google Scholar 

  65. Kawakami, Y., Kawakami, K., Steelant, W.F., Ono, M., Baek, R.C., Handa, K., Withers, D.A., Hakomori, S.: Tetraspanin CD9 is a “proteolipid,” and its interaction with alpha 3 integrin in microdomain is promoted by GM3 ganglioside, leading to inhibition of laminin-5-dependent cell motility. J. Biol. Chem. 277(37), 34349–34358 (2002). doi:10.1074/jbc.M200771200

    Article  CAS  PubMed  Google Scholar 

  66. Lee, L., Abe, A., Shayman, J.A.: Improved inhibitors of glucosylceramide synthase. J. Biol. Chem. 274(21), 14662–14669 (1999)

    Article  CAS  PubMed  Google Scholar 

  67. Toledo, M.S., Suzuki, E., Handa, K., Hakomori, S.: Cell growth regulation through GM3-enriched microdomain (glycosynapse) in human lung embryonal fibroblast WI38 and its oncogenic transformant VA13. J. Biol. Chem. 279(33), 34655–34664 (2004). doi:10.1074/jbc.M403857200

    Article  CAS  PubMed  Google Scholar 

  68. Mitsuzuka, K., Handa, K., Satoh, M., Arai, Y., Hakomori, S.: A specific microdomain (“glycosynapse 3”) controls phenotypic conversion and reversion of bladder cancer cells through GM3-mediated interaction of alpha3beta1 integrin with CD9. J. Biol. Chem. 280(42), 35545–35553 (2005). doi:10.1074/jbc.M505630200

    Article  CAS  PubMed  Google Scholar 

  69. Birchmeier, C., Birchmeier, W., Gherardi, E., Vande Woude, G.F.: Met, metastasis, motility and more. Nat. Rev. Mol. Cell Biol. 4(12), 915–925 (2003). doi:10.1038/nrm1261

    Article  CAS  PubMed  Google Scholar 

  70. Todeschini, A.R., Dos Santos, J.N., Handa, K., Hakomori, S.I.: Ganglioside GM2-tetraspanin CD82 complex inhibits met and its cross-talk with integrins, providing a basis for control of cell motility through glycosynapse. J. Biol. Chem. 282(11), 8123–8133 (2007). doi:10.1074/jbc.M611407200

    Article  CAS  PubMed  Google Scholar 

  71. Todeschini, A.R., Dos Santos, J.N., Handa, K., Hakomori, S.I.: Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway. Proc. Natl. Acad. Sci. U. S. A. 105(6), 1925–1930 (2008). doi:10.1073/pnas.0709619104

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  72. Prinetti, A., Aureli, M., Illuzzi, G., Prioni, S., Nocco, V., Scandroglio, F., Gagliano, N., Tredici, G., Rodriguez-Menendez, V., Chigorno, V., Sonnino, S.: GM3 synthase overexpression results in reduced cell motility and in caveolin-1 upregulation in human ovarian carcinoma cells. Glycobiology 20(1), 62–77 (2010). doi:10.1093/glycob/cwp143

    Article  CAS  PubMed  Google Scholar 

  73. Prinetti, A., Cao, T., Illuzzi, G., Prioni, S., Aureli, M., Gagliano, N., Tredici, G., Rodriguez-Menendez, V., Chigorno, V., Sonnino, S.: A glycosphingolipid/caveolin-1 signaling complex inhibits motility of human ovarian carcinoma cells. J. Biol. Chem. 286(47), 40900–40910 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

Our studies described here were supported mainly by National Cancer Institute Outstanding Investigator Grant (OIG) CA42505 and R01 CA80054, and by The Biomembrane Institute. The authors are grateful to Dr. S. Anderson for English editing of the manuscript

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Hakomori, SI., Handa, K. GM3 and cancer. Glycoconj J 32, 1–8 (2015). https://doi.org/10.1007/s10719-014-9572-4

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