Biochemistry

1975, 3

Graduated from Nagoya University School of Medicine

1975, 5

Internship at Nagoya Higashi Citizen Hospital

1976, 4

Resisdent of Internal Medicine at Nagoya National Hospital

1980, 10

Internist at the 1st Department of Internal Medicine, Nagoya University School of Medicine.

1984, 1

Research Associate, Sloan-Kettering Cancer Research Institute, New York

1989, 2

Assistant Professor, Department of Oncology, Nagasaki University School of Medicine

1990, 4

Associate Professor, Department of Oncology, Nagasaki University School of Medicine

1997, 3

Professor, Department of Biochemistry II, Nagoya University School of Medicine

2000, 4

Professor, Department of Biological Chemistry, Nagoya University Graduate School of Medicine

Regulatory mechanisms for signaling of cancer and neuronal cells with glycosylation

Glycosphingolipids are involved in the regulation of signaling for the cell growth, invasion, differentiation and cell death. We have shown that cancer-associated disialyl-glycolipids are involved in the enhancement of malignant properties in human melanomas, small cell lung cancers and renal cell cancers. On the other hand, monosialyl-gangliosides such as GM1 turned out to suppress malignant phenotypes of cancer cells by regulating intracellular localization of integrins. In the analyses of glycolipid-deficient mutant mice, it has been demonstrated that gangliosides are involved in the maintenance of the integrity of nervous systems and in the repair of damaged nerve tissues. In both cancer cells and nervous systems, it appears that gangliosides are essential in the regulation of signals mediated via lipid rafts, and also in the regulation of the microdomain itself. Therefore, it should be very important to attack molecular complex formed in the vicinity of cell membrane containing glycolipids, integrins, focal adhesion kinases and Src-family kinases as an effective anti-cancer therapeutics. It is also shown that gangliosides might be critical to keep integrity of lipid rafts in vivo, and to maintain signaling for the regulation of nervous systems. On the basis of these results, novel strategies for the therapy of malignant tumors and of neurodegenerative changes are now under investigation.

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3. Matsumoto Y et al. Guillain-Barre syndrome-associated IgG response to gangliosides are generated independently of CD1 function in mice. J. Immunol. 180: 39-43 (2008)
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6. Zhang Q et al. Metastatic potential of mouse Lewis lung cancer cells is regulated via ganglioside GM1 by modulating the matrix metalloprotease-9 localization in lipid rafts. J. Biol. Chem. 281: 18145-18155 (2006)
7. Okuda T et al. Targeted disruption of Gb3/CD77 synthase gene resulted in the complete deletion of globo-series glycosphingolipids and loss of sensitivity to verotoxins. J. Biol. Chem. 281: 10230-10235 (2006)
8. Aixinjueluo W et al. Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies: Roles of anoikis. J. Biol. Chem. 280: 29828-29836 (2005)
9. Hamamura K et al. Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells. Proc. Natl. Acad. Sci. USA 102: 11041-11046 (2005)
10. Kato H et al. RNA polymerase II is required for siRNA generation and peri-centromeric heterochromatin formation in fission yeast. Science 309: 467-469 (2005)
11. Yuki N et al. Carbohydrate Mimicry between Human Ganglioside GM1 and Campylobacter jejuni Lipo-oligosaccharide Causes Guillain-Barré Syndrome. Proc. Natl. Acad. Sci. USA. 101: 11404-11409 (2004)
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13. Tsuchida A et al. Synthesis of disialyl Lewis a structure in colon cancer cell lines by a sialyltransferase ST6GalNAc VI responsible for the synthesis of a-series gangliosides. J. Biol. Chem. 278: 22787-22794 (2003)
14. Mitsuda T et al. Over-expression of ganglioside GM1 results in the dispersion of platelet derived growth factor receptor from glycolipid-enriched micro-domains and in the suppression of cell growth signals. J. Biol. Chem. 277: 11239-11246 (2002)
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16. Okada M et al. b-series ganglioside deficiency exhibits no definite changes in the neurogenesis and the sensitivity to Fas-mediated apotosis, but impairs regeneration of the lesioned hypoglossal nerve. J. Biol. Chem. 277: 1633-1636 (2002)
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19. Takamiya K et al. Mice with disrupted GM2/GD2 synthase gene lack complex gangliosides, but exhibit only subtle defects in their nervous system. Proc. Natl. Acad. Sci. USA. 93: 10662-10667 (1996)