Regulatory mechanism for intracellar traficking of the membrane-bound NEU3 sialidase

• Project/Area Number: 24570142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Miyagi Prefectural Hospital Organization Miyagi Cancer Center
• 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), その他部局等, 研究員 (80373215)
• Co-Investigator(Renkei-kenkyūsha): TANAKA Nobuyuki 宮城県立がんセンター研究所, 部長 (60280872) ; MIYAGI Taeko 東北薬科大学, 分子生体膜研究所, 教授 (50006110)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シアリダーゼ / ガングリオシド / 細胞内輸送 / シグナル伝達 / 細胞膜

Outline of Final Research Achievements

We previously found that activation of EGF receptor signaling triggers translocation of the membrane-bound NEU3 sialidase from cytoplasm to cell membrane, which had not been reported for other glycoenzymes. To gain an insight into the molecular mechanism underlying NEU3 intracellular trafficking, we attempted to identify proteins which can interact with NEU3 in cells. We identified evectin, CAMK1G, MAP1A, and ITM2C as potent candidates for NEU3-binding proteins and got structural information about the interaction. These results could provide an important clue for understanding how NEU3 modulates signal transductions and subsequently affects on pathological conditions such as cancer or diabetes.

Research Products

• [Journal Article] Phosphatidic acid-mediated activation and translocation to the cell surface of sialidase NEU3, promoting signaling for cell migration. (2015)
  • Author(s): Shiozaki K, Takahashi K, Hosono M, Yamaguchi K, Hata K, Shiozaki M, Bassi R, Prinetti A, Sonnino S, Nitta K, Miyagi T.
  • Journal Title: FASEB J Volume: 29 Issue: 5 Pages: 2099-2111
  • DOI: 10.1096/fj.14-262543
  • Peer Reviewed
• [Journal Article] Increased sialidase activity in serum of cancer patients: Identification of sialidase and inhibitor activities in human serum. (2015)
  • Author(s): Hata K, Tochigi T, Sato I, Kawamura S, Shiozaki K, Wada T, Takahashi K, Moriya S, Yamaguchi K, Hosono M, Miyagi T.
  • Journal Title: Cancer Sci Volume: 106 Issue: 4 Pages: 383-389
  • DOI: 10.1111/cas.12627
  • Peer Reviewed
• [Journal Article] Sialidase NEU3 contributes neoplastic potential on colon cancer cells as a key modulator of gangliosides by regulating Wnt signaling. (2015)
  • Author(s): Takahashi K, Hosono M, Sato I, Hata K, Wada T, Yamaguchi K, Nitta K, Shima H, Miyagi T.
  • Journal Title: Int J Cancer Volume: published online Issue: 7 Pages: 00-00
  • DOI: 10.1002/ijc.29527
  • Peer Reviewed
• [Journal Article] Plasma membrane-associated sialidase confers cancer initiation, promotion and progression. (2015)
  • Author(s): Miyagi T, Takahashi K, Shiozaki K, Yamaguchi K, Hosono M
  • Journal Title: Adv Exp Med Biol. Volume: 842 Pages: 139-145
  • DOI: 10.1007/978-3-319-11280-0_9
  • ISBN: 9783319112794, 9783319112800
• [Journal Article] Identification of TL-Om1, an ATL Cell Line, as a Reference Material for Human T-Lymphotropic Virus 1 Quantitative PCR. (2015)
  • Author(s): Kuramitsu M, Okuma K, Yamagishi M, Yamochi T, Firouzi S, Momose H, Mizukami T, Takizawa K, Araki K, Sugamura K, Yamaguchi K, Watanabe T, Hamaguchi I.
  • Journal Title: Journal of Clinical Microbiology Volume: 53 Issue: 2 Pages: 587-596
  • DOI: 10.1128/jcm.02254-14
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Suppressive expression of CD274 increases tumorigenesis and cancer stem cell phenotypes in cholangiocarcinoma. (2014)
  • Author(s): Tamai K, Nakamura M, Mizuma M, Mochizuki M, Yokoyama M, Endo H, Yamaguchi K, Nakagawa T, Shiina M, Unno M, Muramoto K, Sato I, Satoh K, Sugamura K, Tanaka N.
  • Journal Title: Cancer Sci. Volume: Epub
  • Peer Reviewed
• [Journal Article] Enhanced expression of long non-coding RNA HOTAIR is associated with the development of gastric cancer. (2013)
  • Author(s): Endo H, Shiroki T, Nakagawa T, Yokoyama M, Tamai K, Yamanami H, Fujiya T, Sato I, Yamaguchi K, Tanaka N, Iijima K, Shimosegawa T, Sugamura K, Satoh K.
  • Journal Title: PlosONE Volume: 8 Issue: 10 Pages: e77070-e77070
  • DOI: 10.1371/journal.pone.0077070
  • Peer Reviewed
• [Journal Article] CD271 Defines a Stem Cell-Like Population in Hypopharyngeal Cancer (2013)
  • Author(s): Imai T
  • Journal Title: PLoS One Volume: 8 Issue: 4 Pages: e62002-e62002
  • DOI: 10.1371/journal.pone.0062002
  • Peer Reviewed
• [Journal Article] Molecular cloning and biochemical characterization of two novel Neu3 sialidases, neu3a and neu3b, from medaka (Oryzias latipes) (2013)
  • Author(s): Shiozaki K, Takeshita K, Ikeda M, Ikeda A, Harasaki Y, Komatsu M, Yamada S, Yamaguchi K, Miyagi T
  • Journal Title: Biochimie Volume: 95 Issue: 2 Pages: 280-289
  • DOI: 10.1016/j.biochi.2012.09.026
  • Peer Reviewed
• [Journal Article] Reduced susceptibility to colitis-associated colon carcinogenesis in mice lacking plasma membrane-associated sialidase (2012)
  • Author(s): Yamaguchi, K., Shiozaki, K., Moriya, S., Koseki, K., Wada, T., Tateno, H., Sato, I., Asano, M., Iwakura, Y., and Miyagi, T.
  • Journal Title: PLoS ONE Volume: 7 Issue: 7 Pages: e41132-e41132
  • DOI: 10.1371/journal.pone.0041132
  • Peer Reviewed
• [Journal Article] Sialidase NEU4 Hydrolyzes Polysialic Acids of Neural Cell Adhesion Molecules and Negatively Regulates Neurite Formation by Hippocampal Neurons. (2012)
  • Author(s): Takahashi K、ほか７名
  • Journal Title: J Biol Chem. Volume: 287 Issue: 18 Pages: 14816-14826
  • DOI: 10.1074/jbc.m111.324186
  • Peer Reviewed
• [Journal Article] Human cytosolic sialidase NEU2-low general tissue expression but involvementin PC-3 prostate cancer cell survival (2012)
  • Author(s): Koseki K, Wada T, Hosono M, Hata K, Yamaguchi K, Nitta K, Miyagi T
  • Journal Title: Biochem Biophys Res Commun Volume: 428 Issue: 1 Pages: 142-149
  • DOI: 10.1016/j.bbrc.2012.10.028
  • Peer Reviewed
• [Journal Article] Altered expression of sialidases in human cancer (2012)
  • Author(s): Miyagi T, Takahashi K, Moriya S, Hata K, Yamamoto K, Wada T, Yamaguchi K, Shiozaki K
  • Journal Title: Adv Exp Med Biol Volume: 749 Pages: 257-267
  • DOI: 10.1007/978-1-4614-3381-1_17
  • ISBN: 9781461433804, 9781461433811
  • Peer Reviewed
• [Presentation] シアリダーゼはがんの発がん過程と進展に関与する (2014)
  • Author(s): 宮城妙子、高橋耕太、細野雅祐、塩崎一弘、山口壹範
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 免疫不全NOGマウスにより分画された高造腫瘍性ATL細胞の性状解析 (2014)
  • Author(s): 山口壹範、那須健太郎、玉井恵一、佐藤賢一、井根省二、 佐々木治、張替秀郎、田中伸幸、菅村和夫
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] BEX2は静止期がん幹細胞の維持に重要な役割を果たす (2014)
  • Author(s): 玉井恵一、中村真央、望月麻衣、小鎌直子、横山美沙、山口壹範、佐藤賢一、菅村和夫、田中伸幸
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] ピルビン酸キナーゼM2(PKM2)は膵癌で高発現し、細胞増殖能を亢進させる (2014)
  • Author(s): 横山美沙、白木健悠、田沼延公、玉井恵一、山口壹範、田中伸幸、菅村和夫、佐藤賢一
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 免疫不全NOGマウスを用いた高造腫瘍性ATL細胞単離法の開発 (2013)
  • Author(s): 山口壹範、玉井恵一、井上愛、佐藤賢一、井根省二、佐々木治、張替秀郎、田中伸幸、菅村和夫
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] シアリダーゼ異常による大腸がんの進展機構と治療への応用
  • Author(s): 宮城妙子
  • Organizer: 第３１回日本糖質学会年会
  • Place of Presentation: 鹿児島市民文化ホール
• [Presentation] シアリダーゼNEU3は大腸がん細胞のWnt/brta-cateninシグナリングを制御する
  • Author(s): 高橋耕太
  • Organizer: 第８５回日本生化学会
  • Place of Presentation: 福岡国際会議場
• [Book] Mammalian sialidase and tumor development (in Sugar Chains Eds Suzuki T., Ohtsubo K., Taniguchi N.) (2015)
  • Author(s): Miyagi T, Takahashi K, Shiozaki K, Yamaguchi K.
  • Total Pages: 16
  • Publisher: Springer
• [Book] Mammalian sialidases: Sialobiology: Structure, Biosynthesis and Function (2013)
  • Author(s): Suzuki T.
  • Publisher: Bentham Science Publishers