Mechanism of intestinal tumor formation through ADAM10

• Project/Area Number: 26860528
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Keio University
• Principal Investigator: Matano Mami 慶應義塾大学, 医学部, 研究員 (20439889)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 下部消化管学

Outline of Final Research Achievements

Our research group generated an epithelium specific ADAM10 knock-out mice through crossing ADAM10 flox mouse with villin-CreER mice. Tamoxifen induced knock out resulted in increased goblet cells and decreased intestinal stem cells. This can be explained by increased stem cell differentiation.
ADAM10 is involved in Notch signal activation through degradation of the intracellular domain. Indeed, ADAM10 knock-out intestinal epithelium inactivated Notch signal, resulting in loss of intestinal stem cells.

Research Products

• [Journal Article] A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis (2016)
  • Author(s): Fujii M, Shimokawa M, Date S, Takano A, Matano M, Nanki K, Ohta Y, Toshimitsu K, Nakazato Y, Kawasaki K, Uraoka T, Toshiaki T, Watanabe Kanai T, Sato T.
  • Journal Title: Cell Stem Cell Volume: in press
  • Peer Reviewed
• [Journal Article] Active and water-soluble form of lipidated Wnt protein is maintained by a serum glycoprotein afamin/α-albumin. (2016)
  • Author(s): Mihara, E., Hirai, H., Yamamoto, H., Tamura-Kawakami, K., Matano, M., Kikuchi, A., Sato, T., and Takagi, J.
  • Journal Title: Elife Volume: 5 Pages: 1-19
  • DOI: 10.7554/elife.11621
  • Peer Reviewed / Open Access
• [Journal Article] Efficient genetic engineering of human intestinal organoids using electroporation. (2015)
  • Author(s): Fujii M, Matano M, Nanki K, Sato T.
  • Journal Title: Nature Protocols Volume: 10 Issue: 10 Pages: 1474-85
  • DOI: 10.1038/nprot.2015.088
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Sweetness characterization of recombinant human lysozyme. (2015)
  • Author(s): Matano M, Nakajima K, Kashiwagi Y, Udaka S, Maehashi K.
  • Journal Title: Comp Biochem Physiol B Biochem Mol Biol. Volume: 188 Pages: 8-14
  • DOI: 10.1016/j.cbpb.2015.05.009
  • Peer Reviewed
• [Journal Article] Modelling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. (2015)
  • Author(s): Matano M,Date S, Shimokawa M, Takano A, Fujii M, Ohta Y, Watanabe T, Kanai T, Sato T.
  • Journal Title: Nature Medicine Volume: 21(3) Issue: 3 Pages: 256-262
  • DOI: 10.1038/nm.3802
  • Peer Reviewed / Open Access
• [Journal Article] Cross-talk between RORgammat+ innate lymphoid cells and intestinal macrophages induces mucosal IL-22 production in Crohn's disease. (2014)
  • Author(s): 1.Mizuno S, Mikami Y, Kamada N, Handa T, Hayashi A, Sato T, Matsuoka K, Matano M, Ohta Y, Sugita A, Koganei K, Sahara R, Takazoe M, Hisamatsu T, Kanai T.
  • Journal Title: Inflamm Bowel Dis Volume: 20(8) Issue: 8 Pages: 1426-1434
  • DOI: 10.1097/mib.0000000000000105
  • Peer Reviewed
• [Journal Article] Biochemical and functional characterization of transiently expressed in neural precursor (TENP) protein in emu egg white. (2014)
  • Author(s): Maehashi K, Ueda M, Matano M, Takeuchi J, Uchino M, Kashiwagi Y, Watanabe T.
  • Journal Title: J Agric Food Chem. Volume: 62(22) Issue: 22 Pages: 5156-62
  • DOI: 10.1021/jf5008117
  • Peer Reviewed
• [Presentation] The Self-renewing Mechanism of Intestinal Stem Cell: Niche and Cancer (2014)
  • Author(s): Toshiro Sato, Yuki Ohta, Ai Takano, Shoichi Date, Mamiko Matano, Mariko Shimokawa.
  • Organizer: 7th Annual Meeting of the Japanese Society of Developmental Biologists and Asia Pacific Developmental Biology Network
  • Place of Presentation: WINC愛知（名古屋）
  • Year and Date: 2014-05-28