Investigation on the molecular mechanism modulating EGFR signal transduction via the membrane-associated sialidase

• Project/Area Number: 21570122
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所) (2011); Miyagi Cancer Center Research Institute (2009-2010)
• Principal Investigator: YAMAGUCHI Kazunori 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), 発がん制御研究部, 上席主任研究員 (80373215)
• Co-Investigator(Kenkyū-buntansha): TATENO Hiroo 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), 病理部, 部長 (70004744)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 糖質 / シグナル伝達 / シアリダーゼ / 上皮増殖因子 / 糖鎖

Research Abstract

The membrane-associated sialidase NEU3, a kind of glycolytic enzyme, localizes at cell membrane and promotes tumor formation through activation of EGFR. We previously showed that interaction between NEU3 and EGFR plays role in the activation. In this study, we investigated an involvement of NEU3 in colon tumor formation by using Neu3 knock out mice. We also analyzed interaction between NEU3 and EGFR at molecular level

Research Products

• [Journal Article] Mammalian sialidases : physiological and pathological roles in cellular functions (2012)
  • Author(s): Miyagi, T., et al
  • Journal Title: Glycobiology Volume: 22 Issue: 7 Pages: 880-896
  • DOI: 10.1093/glycob/cws057
  • Peer Reviewed
• [Journal Article] Plasma membrane-associated sialidase (NEU3) regulates progression of prostate cancer to androgen-independent growth through modulation of androgen receptor signaling (2012)
  • Author(s): Kawamura, S., et al
  • Journal Title: Cell Death Differ Volume: 19 Issue: 1 Pages: 170-179
  • DOI: 10.1038/cdd.2011.83
  • Peer Reviewed
• [Journal Article] Regulation of Sialyl Lewis Antigen Expression in Colon Cancer Cells by Sialidase NEU4 (2011)
  • Author(s): Shiozaki, K., Yamaguchi, K., Takahashi, K., Moriya, S., Miyagi, T.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 21052-21061
  • Peer Reviewed
• [Journal Article] Regulation of Sialyl Lewis Antigen Expression in Colon Cancer Cells by Sialidase NEU4 (2011)
  • Author(s): Shiozaki, K., et al
  • Journal Title: J Biol Chem Volume: 286 Issue: 24 Pages: 21052-21061
  • DOI: 10.1074/jbc.m111.231191
  • Peer Reviewed
• [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 Volume: 430 Pages: 107-117
  • Peer Reviewed
• [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., Yamaguchi, K., Senda, S., Miyagi, T.(他3名、7番目)
  • Journal Title: Clin. Exp. Immunol Volume: 161 Pages: 233-241
  • Peer Reviewed
• [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: Biochemical Journal Volume: 430 Pages: 107-117
  • Peer Reviewed
• [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, Yamaguchi K, Senda S, Miyagi T
  • Journal Title: Clinical and Experimental Immunology Volume: 161 Pages: 233-241
  • Peer Reviewed
• [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., Miyagi, T.(他2名、3番目)
  • Journal Title: J. Biol. Chem Volume: 284 Pages: 21157-21164
  • 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., Yamaguchi, K., Sato, I., Miyagi, T.
  • Journal Title: Cancer Sci Volume: 100 Pages: 588-594
  • NAID: 10025143974
  • 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., Takahashi, R., Hongo, Y., Koshino, H., Yamaguchi, K., Miyagi, T.
  • Journal Title: J. Org. Chem Volume: 74 Pages: 6382-6385
  • Peer Reviewed
• [Journal Article] Contribution of sialidase NEU1 to suppression of metastasis of human colon cancer cells through desialylation of integrin beta4 (2009)
  • Author(s): Uemura, T., Shiozaki, K., Yamaguchi, K., Miyazaki, S., Satomi, S., Kato, K., Sakuraba, H., Miyagi, T.
  • Journal Title: Oncogene Volume: 28 Pages: 1218-1229
  • 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, Yamaguchi K, Sato I, Miyagi T.
  • Journal Title: Cancer Science 100巻 Pages: 588-594
  • NAID: 10025143974
  • Peer Reviewed
• [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: Journal of Biological Chemistry 284巻 Pages: 21157-21164
  • Peer Reviewed
• [Journal Article] Plasma membrane-associated sialidase(NEU3) regulates progression of prostate cancer to androgen-independent growth through modulation of androgen receptor signaling
  • Author(s): Kawamura, S., Yamaguchi, K., Miyagi, T(他12名、4番目)
  • Journal Title: Cell Death. Differ Volume: (in press)
  • Peer Reviewed
• [Presentation] シアリダーゼNEU3の異常亢進はEGFRシグナリング活性化を介してがんの進展に導く (2011)
  • Author(s): 宮城妙子,高橋耕太,和田正,山口壹範,塩崎一弘,細野雅祐,仁田一雄
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 形質膜シアリダーゼ(NEU3)は癌幹細胞性を制御する (2011)
  • Author(s): 高橋耕太,和田正,山口壹範,細野雅祐,仁田一雄,宮城妙子
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] シアリダーゼNEU3はARシグナリング修飾を介して前立腺癌のアンドロゲン非依存性増殖への進展を制御する (2011)
  • Author(s): 佐藤郁朗,川村貞文,栃木達夫,和田正,山口壹範,高橋耕太,宮城妙子
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 形質膜シアリダーゼNEU3の膜トポロジーに関する研究 (2011)
  • Author(s): 秦敬子,和田正,橋井則貴,川崎ナナ,塩崎一弘,山口壹範,高橋耕太,森谷節子,細野雅祐,仁田一雄,宮城妙子
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-21
• [Presentation] メダカシアリダーゼNeu3のクローニングおよび性状解析 (2011)
  • Author(s): 塩崎一弘,竹下一輝,池田真子,小松正治,山田章二,山口壹範,宮城妙子
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-21
• [Presentation] Plasma membrane-associated sialidase (NEU3) regulates progression of prostate cancer through modulation of androgen receptor signaling (2011)
  • Author(s): Miyagi, T.
  • Organizer: 21st International Symposium on Glycoconjugates
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2011-08-22
• [Presentation] Plasma membrane-associated sialidase(NEU3) regulates progression of prostate cancer through modulation of androgen receptor signaling (2011)
  • Author(s): Kawamura S., Sato I., Wada T., Yamaguchi K., Moriya S., Miyagi T.
  • Organizer: 21st International Symposium on Glycoconjugates
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2011-08-21
• [Presentation] シアリダーゼNeu4による神経接着分子NCAMポリシアル酸分解の制御 (2010)
  • Author(s): 高橋耕太,塩崎一弘,山口壹範,森谷節子,宮城妙子
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] シアリダーゼNEU3によるEGFRシグナリング活性化機構の解析 (2010)
  • Author(s): 秦敬子,和田正,山口壹範,高橋耕太,森谷節子,塩崎一弘,宮城妙子
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] Sialidase NEU4 attenuates E-selectin derived signaling in colon cancer cells (2010)
  • Author(s): Shiozaki, K., Yamaguchi, K., Takahashi, K., and Miyagi, T.
  • Organizer: Sialoglyco meeting
  • Place of Presentation: Potsdam, Germany
  • Year and Date: 2010-08-21
• [Presentation] Activation of plasma membrane-associated sialidase NEU3 by phospholipid (2010)
  • Author(s): Shiozaki, K., Hata, K., Yamaguchi, K., and Miyagi, T.
  • Organizer: The 28th Naito Conference on Glycan Expression and Regulation[I] Functions and Disease Mechanisms
  • Place of Presentation: Hayama, Japan
  • Year and Date: 2010-07-27
• [Presentation] シアリダーゼNEU3はフォスファチジン酸により活性化される (2010)
  • Author(s): 塩崎一弘,山口壹範,宮城妙子
  • Organizer: 生理学研究所研究会糖鎖機能研究会
  • Place of Presentation: 岡崎
  • Year and Date: 2010-07-01
• [Presentation] 形質膜シアリダーゼノックアウトマウスにおける大腸がん発症の抑制 (2009)
  • Author(s): 山口壹範
  • Organizer: 東北糖鎖研究会
  • Place of Presentation: 長岡技術科学大学マルチメディアシステムセンター(長岡)
  • Year and Date: 2009-11-20
• [Presentation] Plasma membrane-associated sialidase influences on AOM-induced mouse colon carcinogenesis (2009)
  • Author(s): 山口壹範
  • Organizer: 日本がん学会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2009-10-02
• [Book] 生物機能モデルと新しいリソース・リサーチツール (2011)
  • Author(s): 山口壹範、宮城妙子(分担執筆者)
  • Publisher: エル.アイ.シーシアリダーゼ
• [Book] シアリダーゼ、生物機能モデルと新しいリソース・リサーチツール (2011)
  • Author(s): 山口壹範
  • Publisher: エル・アイ・シー
• [Remarks]
  • URL: http://www.cbt.med.tohoku.ac.jp/member2.html
• [Remarks]
  • URL: http://www.miyagi-pho.jp/mcc/kenkyu/hatugan-seigyo.html