Pathogenesis of cancer and diabetes caused by aberrant expression of sialidase

• Project/Area Number: 22659082
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Tohoku Pharmaceutical University
• Principal Investigator: MIYAGI Taeko 東北薬科大学, 大学院・薬学研究科, 教授 (50006110)
• Co-Investigator(Kenkyū-buntansha): SATO Ikurou 宮城県立がんセンター, 病理部, 部長 (50225918) ; SIOZAKI Kazuhiro 鹿児島大学, 水産学部, 助教 (70390896)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,030,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,600,000 (Direct Cost: ¥1,600,000)
• Keywords: 腫瘍 / シアリダーゼ / 癌 / 糖尿病 / 酵素 / 糖鎖 / 遺伝子

Research Abstract

Plasma membrane-associated sialidase is up-regulated in various human cancers including colon cancer. The transgenic mice develop hyperinsulinemia and subsequently insulin resistance, and also are susceptible to induction of colonic aberrant crypt foci by a carcinogen, azoxymethane. Analysis of the pathogenesis revealed that NEU3 activates Wnt signaling, which is thought to be important for cancer progression and also for beta cell growth in pancreatic islets, suggesting an influence of NEU3 on the two diseases probably via Wnt activation.

Research Products

• [Journal Article] Plasma membraneassociated sialidase(NEU3) regulates progression of prostate cancer to androgen-independent growth through modulation of androgen receptor signaling (2012)
  • Author(s): Kawamura, S., Sato, I., Wada, T., Yamaguchi, K., Li, Y., Li, D., Zhao, X., Ueno, S., Aoki, H., Tochigi, T., Kuwahara, M. Kitagawa, T., Takahashi, K., Moriya, S., Miyagi, T
  • Journal Title: Cell Death Differ Volume: 19 Pages: 170-179
• [Journal Article] Mammalian sialidases : physiological and pathological roles in cellular functions (2012)
  • Author(s): Miyagi, T., Yamaguchi, K
  • Journal Title: Glycobiology Volume: 22 Pages: 880-896
• [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 Pages: 170-179
  • Peer Reviewed
• [Journal Article] Membrane sialidase NEU3 is highly expressed in human melanoma cells promoting cell growth with minimal changes in the composition of gangliosides (2011)
  • Author(s): Miyata, M., Kambe, M., Tajima, O., Moriya, S., Sawaki, H., Hotta, H., Kondo, Y., Narimatsu, H., Miyagi, T., Furukawa, K., Furukawa, K
  • Journal Title: Cancer Sci Volume: 102 Pages: 2139-2149
  • NAID: 10030245717
• [Journal Article] Regulation of sialyl Lewis antigen expression in colon cancer cells by sialidase NEU4 (2011)
  • Author(s): Shiozaki, K., Yamaguchi, K., Takahashi, K., MoriyaS., Miyagi, T
  • Journal Title: J. Biol Chem Volume: 286 Pages: 21052-21061
• [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 Pages: 21052-21061
  • 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
• [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 Volume: 161 Pages: 233-241
• [Journal Article] Mammalian sialidases and their functions (2010)
  • Author(s): Miyagi T
  • Journal Title: Trends In Clycoscien and Glycotechnology Volume: 22 Pages: 162-172
  • NAID: 10027508537
• [Journal Article] A crucial role of sialidase Neul in hyaluronan receptor function of CD44 in Thelper type 2-mediated airway inflammation of murine acute asthmatic model. (2010)
  • Author(s): Kato S., et al
  • 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., et al
  • Journal Title: Biochem.J. Volume: 430 Pages: 107-117
  • Peer Reviewed
• [Journal Article] Use of structure-based virtual screening in the investigation of novel human sialidase inhibitors (2010)
  • Author(s): Magesh S., et al
  • Journal Title: Med.Chem.Res. Volume: 19 Pages: 1273-1286
  • Peer Reviewed
• [Journal Article] Mammalian sialidases and their functions. (2010)
  • Author(s): Miyagi T.
  • Journal Title: Trends Glycosci.Glyc Volume: 22 Pages: 162-172
  • NAID: 10027508537
  • Peer Reviewed
• [Presentation] Distinct functional roles between ganglioside sialidases Neu3 and Neu4 (2011)
  • Author(s): Miyagi, T., Yamaguchi, K., Shiozaki, K., Takahashi, K., Wada, T., Hata, K., Moriya, S., Yamamoto, K
  • Organizer: The 31st Naito Conference : Glycan Expression and Regulation[II]: Metabolites, Stress Response, Microdomains, and Beyond
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 2011-09-14
• [Presentation] Distinct functional roles between ganglioside sialidases Neu3 and Neu4 (2011)
  • Author(s): Miyagi, T., et al
  • Organizer: The 31st Naito Conference : Glycan Expression and Regulation [II] : Metabolites, Stress Response, Microdomains, and Beyond
  • Place of Presentation: Chateraise Gateaux Kingdom, Sapporo, Japan(招待講演)
  • Year and Date: 2011-09-14
• [Presentation] Aberrant expression of sialidase and cancer progression (2011)
  • Author(s): Miyagi, T
  • Organizer: US-JAPA Conference : Inflammation, Diabetes, And Cancer
  • Place of Presentation: City of Hope, Duarte CA, USA
  • Year and Date: 2011-08-04
• [Presentation] Aberrant expression of sialidase and cancer progression (2011)
  • Author(s): Miyagi, T.
  • Organizer: US-JAPAN Conference : Inflammation, Diabetes and Cancer
  • Place of Presentation: City Of Hope, Duarte, CA, USA(招待講演)
  • Year and Date: 2011-08-04
• [Presentation] がんで過剰発現する形質膜シアリダーゼNEU3の悪性化進展機構 (2011)
  • Author(s): 宮城妙子, ら
  • Organizer: 日本糖質学会
  • Place of Presentation: 長岡(長岡リリックホール)
  • Year and Date: 2011-07-12
• [Presentation] がん幹細胞様形質発現におけるシアリダーゼNEU3の役割 (2011)
  • Author(s): 宮城妙子
  • Organizer: 日本がん転移学会
  • Place of Presentation: 浜松(アクトシティ浜松)
  • Year and Date: 2011-06-30
• [Presentation] Altered expression of sialidases in human cancer (2011)
  • Author(s): Miyagi, T., Takahashi, K., Moriya, S., Hata, K., Wada, T., Yamaguchi, K., Shiozaki, K
  • Organizer: IXth International Symposium(IXth ISCSM, 2011) on "Biochemical Roles of Eukaryotic Cell Surface Macromolecules"
  • Place of Presentation: Trivandrum, India
  • Year and Date: 2011-01-28
• [Presentation] Altered expression of sialidases in human cancer (2011)
  • Author(s): Miyagi T., et al
  • Organizer: IXth International Symposium (IXth ISCSM, 2011)
  • Place of Presentation: Trivandrum, India
  • Year and Date: 2011-01-28
• [Presentation] Sialidase NEU4 attenuates E-selectin derived signaling in colon cancer cells (2010)
  • Author(s): Miyagi T., et al
  • Organizer: SIALOGLYCO 2010
  • Place of Presentation: Potsdam, Germany.
  • Year and Date: 2010-08-25
• [Book] Structure and function of mammalian sialidases. in Topics in Current Chemistry : Sialoglyco-Biology and-Chemistry
  • Author(s): Monti, E. and Miyagi, T
  • Publisher: Springer(in press)
• [Book] Altered expression of sialidases in human cancer. Proceedings of the 9th ISCSM
  • Author(s): Miyagi T., Takahashi K., Moriya S., Hata K., Wada T. Yamaguchi K., Shiozaki K
  • Publisher: Springer Publishers(in press)
• [Remarks]
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/ganseigyo/index.html
• [Remarks]
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/ganseigyo/index.html
• [Remarks]
  • URL: http://www.tohoku-pharm.ac.jp/laboratory/ganseigyo/index.html