The role of cell cycle regulator Cdh1 in carcinogenesis and development of gastrointestinal cancer.

• Project/Area Number: 23590980
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Kumamoto University
• Principal Investigator: NAOE Hideaki 熊本大学, 医学部附属病院, 助教 (30599246)
• Co-Investigator(Kenkyū-buntansha): SASAKI Yutaka 熊本大学, 大学院生命科学研究部, 教授 (70235282) ; YOKOMINE Kazunori 熊本大学, 医学部付属病院, 助教 (60530128) ; FUJIMOTO Jirou 兵庫医科大学, 医学部, 教授 (90199373)
• Co-Investigator(Renkei-kenkyūsha): SAYA Hideyuki 慶應義塾大学, 医学部, 教授 (80264282)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 肝臓学 / pathway解析 / 大腸癌 / 浸潤・転移 / 消化器癌 / 細胞骨格 / 細胞運動

Research Abstract

Suppress the expression of Cdh1 with siRNA tequnique in colon cancer cell line. These cells revealed cytoskeletal abnormality with decreased actin filament.In the analysis of cell motility with the wound healing assay, Cdh1 suppresse cells showed high motility compared with the control cells.
Next, we generated heterogenous mice which one of the phosphorylation site of Cdh1 was suppressed with gene trap tequnique.Genotyping of offspring of these mice was following as wild type: hetero: homo=13:32:0. These results indicated that homo suppression of Cdh1 phosphorylation site was embryonic lethal event in mice.Now,we are studying about the timing of lethality and cause of death.

Research Products

• [Journal Article] The APC/C activator Cdh1 regulates the G2/M transition during differentiation of placental trophoblast stem cells (2013)
  • Author(s): Naoe H, Chiyoda T, Ishizawa J, Masuda K, Saya H, Kuninaka S
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 430(2) Pages: 757-62
  • Peer Reviewed
• [Journal Article] Primary hepatic gastrinoma as an unusual manifestation of Zollinger-Ellison syndrome (2012)
  • Author(s): Naoe H, Iwasaki H, Kawasaki T, Ozaki T, Tsutsumi H, Okuda A, Konoe T, Nonaka K, Kaku E, Shono T, Yokomine K, Sakurai K, Iyama K, Hirota M, Sasaki Y
  • Journal Title: Case Reports in Gastroenterology Volume: 6 Issue: 3 Pages: 590-595
  • DOI: 10.1159/000343157
  • Peer Reviewed
• [Journal Article] LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression (2012)
  • Author(s): Chiyoda T, Sugiyama N, Shimizu T, Naoe H, Kobayashi Y, Ishizawa J, Arima Y, Tsuda H, Ito M, Kaibuchi K, Aoki D, Ishihama Y, Saya H, and Kuninaka S.
  • Journal Title: Journal of Cell Biology Volume: in press
  • Peer Reviewed
• [Journal Article] The cell cycle regulator Cdh1 controls the pool sizes of hematopoietic stem cells and mature lineage progenitors by protecting from genotoxic stress (2011)
  • Author(s): Ishizawa J, Kuninaka S, Sugihara E, Naoe H, Kobayashi Y, Chiyoda T, Ueki A, Araki K, Yamamura KI, Matsuzaki Y, Nakajima H, Ikeda Y, Okamoto S, Saya H.
  • Journal Title: Cancer Science Volume: 22 Pages: 1-8
  • NAID: 10029293305
  • Peer Reviewed
• [Journal Article] Establishment of a Choriocarcinoma Model from Immortalized Normal Extravillous Trophoblast Cells Transduced with HRASV12 (2011)
  • Author(s): Kobayashi Y, Shimizu T, Naoe H, Ueki A, Ishizawa J, Chiyoda T, Onishi N, Sugihara E, Nagano O, Banno K, Kuninaka S, Aoki D, Saya H.
  • Journal Title: The American Journal of Pathology Volume: 179 Pages: 1471-1482
  • Peer Reviewed
• [Presentation] 肝癌の治療抵抗性を担う新規分子マーカーの解析 (2013)
  • Author(s): 直江秀昭、田中基彦、佐々木 裕
  • Organizer: 第99回 日本消化器病学会総会
  • Place of Presentation: 鹿児島、城山観光ホテル
• [Presentation] An integrated approach of differential mass spectrometry and gene ontology analysis can identify key molecules regulating apoptosis resistance in human hepatoma cells (2012)
  • Author(s): Naoe H, Hoshida Y, Hirota Y, Yokote S, Nagaoka K, Watanabe T, Yamada Y, Tsuruta Y, Tanaka M, Araki N, Sasaki Y
  • Organizer: The 63^<rd> annual meeting of the American association for the study of liver diseases
  • Place of Presentation: Boston, USA
• [Presentation] 酸化ストレスに対する肝細胞癌の細胞死抵抗性の検討 (2012)
  • Author(s): 直江秀昭、田中基彦、佐々木 裕
  • Organizer: 第20回 日本消化器病学会週間(JDDW)
  • Place of Presentation: 神戸 ポートピアホテル
• [Presentation] An integrated approach of differential mass spectrometry and gene ontology analysis can identify key molecules regulating apoptosis resistance in human hepatoma cells (2012)
  • Author(s): 直江秀昭、星田陽明、横手誠一郎、長岡克弥、山田裕希、渡辺丈久、田中基彦、荒木令江、佐々木 裕
  • Organizer: The 63rd Annual Meeting of the American Association for the Study of Liver Disease
  • Place of Presentation: Boston, USA、プルデンシャルセンタービル
• [Presentation] 遺伝子解析と蛋白質機能解析による肝癌の細胞死抵抗性の解明 ワークショップ「DNA・マイクロRNA解析から消化器疾患の診断・治療・病態解明」 (2011)
  • Author(s): 直江秀昭、田中基彦、佐々木 裕
  • Organizer: 第97回日本消化器病学会総会
  • Place of Presentation: 東京（京王プラザホテル）