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

• 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
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥16,000,000 (Direct Cost: ¥16,000,000); Fiscal Year 2009: ¥8,000,000 (Direct Cost: ¥8,000,000); Fiscal Year 2008: ¥8,000,000 (Direct Cost: ¥8,000,000)
• 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 / siRNA

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
  • NAID: 10025143974
• [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] Developmental change of sialidase NEU4 expression in murine brain and its involvement in the regulation of neuronal cell differentiation (2009)
  • Author(s): Shiozaki, K.et al.
  • Journal Title: J.Biol.Chem. 284巻 Pages: 21157-21164
  • Peer Reviewed
• [Journal Article] Plasma membrane-associated sialidase(NEU3)promotes formation ofcolonic aberrant crypt foci in azoxymethane-treated transgenic mice (2009)
  • Author(s): Shiozaki K., et al.
  • Journal Title: Cancer Sci 100巻 Pages: 588-594
  • Peer Reviewed
• [Journal Article] Contribution of sialidase NEU1 to suppression of metastasis of human colon cancer cells through desialylation of integrin β4 (2009)
  • Author(s): Uemura T., et al.
  • Journal Title: Oncogene 28巻 Pages: 1218-1229
  • Peer Reviewed
• [Journal Article] A strategy for constructing C-sialosides based on Ireland-Claisen rearrangement and its application for synthesis of CF_2-linked ganglioside GM4 analogue (2009)
  • Author(s): Sodeoka M, et al.
  • Journal Title: Pure Applied Chem. 81巻 Pages: 205-215
  • Peer Reviewed
• [Journal Article] Synthesis of all possible isomers corresponding to the proposed structure of montanacin e, and their antitumor activity (2009)
  • Author(s): Takahashi S, et al.
  • Journal Title: J Org Chem. 74巻 Pages: 6382-6385
  • Peer Reviewed
• [Journal Article] Human sialidase inhibitors : design, synthesis, and biological evaluation of 4-acetamido-5-acylamido- 2-fluoro benzoic acids (2009)
  • Author(s): Magesh S, et al.
  • Journal Title: Bioorg Med Chem 17巻 Pages: 4595-4603
  • Peer Reviewed
• [Journal Article] Sialidase occurs in both membranes of the nuclear envelope and hydrolyzes endogenous GD1a (2009)
  • Author(s): Wang J, et al.
  • Journal Title: J Neurochem. 111巻 Pages: 547-554
  • Peer Reviewed
• [Journal Article] A strategy for constructing C-sialosides based on Ireland-Claisen rearrangement and its application for synthesis of CF_2-linked ganglioside GM4 analogue (2009)
  • Author(s): Sodeoka M, et al.
  • Journal Title: Pure Applied Chem. 81 Pages: 205-215
  • Peer Reviewed
• [Journal Article] Plasma membrane -associated sialidase (NEU3) promotes formation of colonic aberrant crypt foci in azoxymethane-treated transgenic mice (2009)
  • Author(s): Shiozaki K., et al.
  • Journal Title: Cancer Sci 100 Pages: 588-594
  • NAID: 10025143974
  • Peer Reviewed
• [Journal Article] Contribution of sialidase NEU1 to suppression of metastasis of human colon cancer cells through desialylation of integrin β4 (2009)
  • Author(s): Uemura T., et al.
  • Journal Title: Oncogene 28 Pages: 1218-1229
  • Peer Reviewed
• [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
  • NAID: 130000093946
• [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
  • NAID: 10021190601
• [Journal Article] Human sialidase as a cancer marker. (2008)
  • Author(s): Miyagi, T., et al.
  • Journal Title: Proteomics 8 Pages: 3303-3311
  • Peer Reviewed
• [Journal Article] Plasma membane-associated sialidase as a crucial regulator of transmenbrane signaling (2008)
  • Author(s): Miyagi, T., et al.
  • Journal Title: J Biochem 144 Pages: 279-285
  • Peer Reviewed
• [Journal Article] Limited Inhibitory Effects of Oseltamivir and Zanamivir on Human Sialidases (2008)
  • Author(s): Hata K., et al
  • Journal Title: Antimicrob.Agents Chemother 52 Pages: 3484-3491
  • Peer Reviewed
• [Journal Article] Aberrant expression of sialidase and cancer progression (2008)
  • Author(s): Miyagi T.
  • Journal Title: Proc Jpn Acad 84 Pages: 407-418
  • NAID: 130000093946
  • Peer Reviewed
• [Journal Article] Synthesis of CH_2-Linke a(2,3) sialyl-galactose analogue : on the stereoselectivity of the key Ireland-Claisen Rearrangement (2008)
  • Author(s): Watanabe T., et al.
  • Journal Title: Org.Lett. 10 Pages: 4167-4170
  • Peer Reviewed
• [Presentation] Role of sialidase NEU3 in prostate cancer progression and its potential utility as a novel; therapeutic target.Clinical and translational Research on cancer: (2009)
  • Author(s): Miyagi T.
  • Organizer: Glycomics applications.
  • Place of Presentation: Toba, Mie
  • Year and Date: 2009-03-25
• [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: Fukusima
  • Year and Date: 2009-03-22
• [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
• [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
• [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, Japan
• [Presentation] A.possible mechanism of NEU3 activation at plasma membrane. (2008)
  • Author(s): Shiozaki, K., et al.
  • Organizer: BMB 2008(第81回日本生化学会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] NEU3 possibly interacts with EGFR at cytoplasmic side of plasma membrane. (2008)
  • Author(s): Shiozaki, M., et al.
  • Organizer: BMB 2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Involvement of plasma-membrane associated sialidase NEU3 in Wnt/beta-catenin signaling. (2008)
  • Author(s): Hata, K., et al.
  • Organizer: BMB 2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Gene structure and transcriptional control of human NEU3 gene. (2008)
  • Author(s): Yamaguchi, K., et al.
  • Organizer: BMB 2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Sialidase research targeted to cancer diagnosis and therapy (2008)
  • Author(s): Miyagi, T., et al.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-30
• [Presentation] Activation of Met receptor-derived signaling by plasma membrane-associated sialidase (NEU3). (2008)
  • Author(s): Shiozaki, K., et al.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] Implication of expression of Neu3 gene in human melanoma cells. (2008)
  • Author(s): Furukawa, K., et al.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] Regulation of Wnt/beta-catenin signaling by plasma membrane-associated sialidase (NEU3). (2008)
  • Author(s): Wada, T., et al.
  • Organizer: 第67回日本癌学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] Crucial roles of plasma membrane-associated sialidase in human cancer (2008)
  • Author(s): Miyagi T., et al.
  • Organizer: 13^<th> World Congress on advances in Oncology
  • Place of Presentation: Crete, Greece
  • Year and Date: 2008-10-10
• [Presentation] CF2-連結型GM4の合成と活性 (2008)
  • Author(s): 平井剛, ら
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-20
• [Presentation] シアリダーゼNEU1によるがん細胞の浸潤・転移抑制機構 (2008)
  • Author(s): 上村卓嗣, ら
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-19
• [Presentation] ヒト細胞質型シアリダーゼNEU2の生理機能解析 (2008)
  • Author(s): 小関弘恵知, ら
  • Organizer: 第28回日本糖質学会年会
  • Place of Presentation: つくば
  • Year and Date: 2008-08-19
• [Presentation] ヒトNEU3シアリダーゼ遺伝子のプロモーター領域の解析、 (2008)
  • Author(s): 山口壹範, ら
  • Organizer: 日本生化学会東北支部会
  • Place of Presentation: 盛岡
  • Year and Date: 2008-05-17
• [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
• [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
  • 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.
  • 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
• [Remarks]
  • URL: http://www.pref.miyagi.jp/mcc/htdocs/kenkyu/seikagaku.html
• [Remarks]
  • URL: http://www.pref.miyagi.jp/mcc/htdocs/kenkyu/seikagaku.html