Molecular mechanism of regulation of cancer cell apoptosis by plasma membrane-associated sialidase

2009 Fiscal Year Final Research Report

• Project/Area Number: 20013047
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: 宮城県立がんセンター研究所 (2009); Miyagi Cancer Center Research Institute (2008)
• Principal Investigator: MIYAGI Taeko 宮城県立がんセンター研究所, 部長兼所長 (50006110)
• Co-Investigator(Kenkyū-buntansha): 塩崎 一弘 宮城県立がんセンター研究所, 博士研究員 (70390896)
• Research Collaborator: 山口 壹範 宮城県立がんセンター研究所, 副主任研究員 ; 和田 正 宮城県立がんセンター研究所, 研究員 ; 川村 貞文 宮城県立がんセンター, 医療部長 ; 佐藤 雅美 宮城県立がんセンター, 医療部長
• Project Period (FY): 2008 – 2009
• Keywords: シアリダーゼ / 糖鎖 / 酵素 / 遺伝子 / ガングリオシド / 情報伝達 / がん治療

Research Abstract

Aberrant sialylation is a characteristic feature associated with malignant properties, including invasiveness and metastatic potential. To elucidate the mechanism and provide valuable new information for diagnosis and therapy, our studies have focused on sialidase, a key enzyme for degradation of sialic acid-containing compounds. Our present study has revealed that plasma membrane-associated sialidase is markedly up-regulated in various human cancers and leads to suppression of apoptosis of cancer cells through activation of cell growth signaling pathway.

Research Products

• [Journal Article] Regulation of plasma membrane-associated sialidase NEU3 gene by Sp1/Sp3 transcription factors (2010)
  • Author(s): Yamaguchi, K., Koseki, K., Shiozaki, M., Shimada, Y., Wada, T., Miyagi, T.
  • Journal Title: Biochem, J. (in press)
• [Journal Article] A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2- mediated airway inflammation of murine acute asthmatic model (2010)
  • Author(s): Katoh S, Maeda S, Fukuoka H, Wada T, Moriya S, Mori A, Yamaguchi K, Senda S, Miyagi T.
  • Journal Title: Clin Exp Immunol (in press)
• [Journal Article] Developmental change of sialidase NEU4 expression in murine brain and its involvement in the regulation of neuronal cell differentiation (2009)
  • Author(s): Shiozaki K, Koseki K, Yamaguchi K, Shiozaki M, Narimatsu H, Miyagi T.
  • Journal Title: J. Biol. Chem. 284 Pages: 21157-21164
• [Journal Article] Sialidase occurs in both membranes of the nuclear envelope and hydrolyzes endogenous gd1a (2009)
  • Author(s): Wang J, Wu G, Miyagi T, Lu ZH, Ledeen RW.
  • Journal Title: J Neurochem 111 Pages: 547-554
• [Journal Article] Plasma membrane -associated sialidase (NEU3) promotes formation of colonic aberrant crypt foci in azoxymethane-treated transgenic mice (2009)
  • Author(s): Shiozaki, K., Yamaguchi, K., Sato, I., Miyagi, T.
  • Journal Title: Cancer Sci. 100 Pages: 588-594
• [Journal Article] Contribution of sialidase NEU1 to suppression of metastasis of human colon cancer cells through desialylation of integrin beta 4 (2009)
  • Author(s): Uemura, T, Shiozaki, K., Yamaguchi, K., Miyazaki, S., Satomi, S., Kato, K., Sakuraba, H., Miyagi, T.
  • Journal Title: Oncogene 28 Pages: 1218-1229
• [Journal Article] Synthesis of all possible isomers corresponding to the proposed structure of montanacin e, and their antitumor activity (2009)
  • Author(s): Takahashi S, Takahashi R, Hongo Y, Koshino H, Yamaguchi K, Miyagi T
  • Journal Title: J Org Chem. 74 Pages: 6382-6385
• [Journal Article] Human sialidase inhibitors: design, synthesis, and biological evaluation of 4-acetamido-5-acylamido- 2-fluoro benzoic acids (2009)
  • Author(s): Magesh S, Savita V, Moriya S, Suzuki T, Miyagi T, Ishida H, Kiso M.
  • Journal Title: Bioorg Med Chem. 17 Pages: 4595-603
• [Journal Article] A strategy for constructing C-sialosides based on Ireland-Claisen rearrangement and its application for synthesis of CF2-linked ganglioside GM4 analogue (2009)
  • Author(s): Sodeoka, M., Hirai, G., Watanabe, T., Miyagi, T.
  • Journal Title: Pure Applied Chem. 81 Pages: 205-215
• [Journal Article] Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human Sialidases. Antimicrob (2008)
  • Author(s): Hata, K., Koseki, K., Yamaguchi, K., Moriya, S., Suzuki, Y., Yingsakmongkon, S., Hirai, G., Sodeoka, M., von Itzstein, M., Miyagi, T.
  • Journal Title: Agents Chemother. 25 Pages: 3484-3491
• [Journal Article] Minireview, Plasma membrane - associated sialidase as a crucial regulator of transmenbrane signaling (2008)
  • Author(s): Miyagi, T., Wada, T., Yamaguchi, K., Hata, H., Shiozaki, K.
  • Journal Title: J. Biochem 144 Pages: 79-285
• [Journal Article] Human sialidase as a cancer marker (2008)
  • Author(s): Miyagi, T., Wada T., Yamaguchi, K., Shiozaki, K., Sato, I., Yamanami, H., Kakugawa, Y., Fujiya, T.
  • Journal Title: Proteomics 8 Pages: 3303-3311
• [Journal Article] Synthesis of CH2-Linked a(2, 3)Sialylgalactose Analogue: on the stereoselectivity of the Key Ireland-Claisen rearrangement (2008)
  • Author(s): Watanabe, T., Hirai, G., Kato, M., Hashizume, D., Miyagi, T., Sodeoka, M.
  • Journal Title: Org. Lett. 10 Pages: 4167-4170
• [Journal Article] Roles of plasma membrane-associated sialidase NEU3 in human cancers (2008)
  • Author(s): Miyagi, T. Wada, T., Yamaguchi, K.
  • Journal Title: Biochim. Biophys. Acta 1780 Pages: 532-537
• [Journal Article] Aberrant expression of sialidase and cancer progression (2008)
  • Author(s): Miyagi, T.
  • Journal Title: Proc Jpn Acad Ser B 84 Pages: 407-418
• [Journal Article] シアリダーゼによる細胞機能の制御とその異常 (2008)
  • Author(s): 宮城妙子
  • Journal Title: 生化学 80 Pages: 13-23
• [Presentation] Sialidase Neu4 contributes to attenuation of E-selectin-derived signaling in colon cancer cells (2009)
  • Author(s): Miyagi T.
  • Organizer: Tohoku carbohydrate minisymposium
  • Place of Presentation: Fukushima
  • Year and Date: 20090300
• [Presentation] Role of sialidase NEU3 in prostate cancer progression and its potential utility as a novel; therapeutic target (2009)
  • Author(s): Miyagi T.
  • Organizer: Clinical and translational Research on cancer: Glycomics Applications
  • Place of Presentation: Toba, Mie
  • Year and Date: 20090300
• [Presentation] Crucial roles of plasma membrane-associated sialidase in human cancer (2008)
  • Author(s): Miyagi, T., Wada, T., Yamaguchi, K, Hata, K., Shiozaki, K.
  • Organizer: 13th World Congress on advances in Oncology
  • Place of Presentation: Crete, Greece
  • Year and Date: 20081000
• [Book] 第3の生命鎖、糖鎖の謎が今、解る(古川鋼一編, 糖鎖異常が招くがんの危険な性質-特にシアリダーゼ異常に着目して) (2009)
  • Author(s): 宮城妙子
  • Total Pages: 78-84
  • Publisher: クバプロ
• [Book] Glycobiology.(Edited by Taniguchi, N., Suzuki, A. and Ito, Y., Sialidase gene In Experimental Glycoscience.) (2008)
  • Author(s): Miyagi, T.
  • Total Pages: 115-118
  • Publisher: Springer Japan
• [Book] Experimental Glycoscience. Glycobiology.(Edited by Taniguchi, N., Suzuki, A. and Ito, Y., Aberrant expression of sialidase in cancer and diabetes.) (2008)
  • Author(s): Miyagi, T.
  • Publisher: Springer Japan
• [Remarks]
  • URL: http://www.pref.miyagi.jp/mcc/htdocs/kenkyu/seikagaku.html