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Block of proliferation and survival of colon cancer cells by intestine-specific homeoprotein CDX2

Research Project

Project/Area Number 24680091
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Tumor biology
Research InstitutionUniversity of Fukui

Principal Investigator

Aoki Koji  福井大学, 学術研究院医学系部門, 教授 (40402862)

Project Period (FY) 2012-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥26,780,000 (Direct Cost: ¥20,600,000、Indirect Cost: ¥6,180,000)
Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2013: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
KeywordsCDX2 / 大腸癌 / オートファジー / ATG7 / ROS / 細胞生存 / 活性酸素 / 増殖 / 細胞増殖 / 細胞死 / 細胞周期
Outline of Final Research Achievements

In this study, we have found that intestine-specific homeoprotein CDX2 bound to ATG7, an essential enzyme for autophagy, directly via its homeodomain and that CDX2 stimulated autophagy in colon cancer cells. We have also found that CDX2 strongly suppressed proliferation and survival of colon cancer cells through autophagy activation. Notably, inhibition of cancer cell proliferation and survival by CDX2 were mediated by increased levels of reactive oxygen species (ROS) caused through autophagy activation. Interestingly, CDX2 increased levels o ROS and suppressed cancer cell survival upon its detachment more strongly than attachment. These results have suggested that CDX2 blocked malignant progression of colon cancer cells including metastasis as well as tumor development.

Report

(6 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (14 results)

All 2016 2015 2014 2012

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (8 results) Book (1 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Mitochondrial function provides instructive signals for activation-induced B cell fates2015

    • Author(s)
      Kyoung-Jin Jang, Hiroto Mano, Koji Aoki, Tatsunari Hayashi, Yukiko Nambu, Eri Hara, Katsu Takahashi, Katsuhiko Itoh, Shigeru Taketani, Kazuhiko Igarashi, Akira Shimizu and Manabu Sugai
    • Journal Title

      Nature Commun

      Volume: 6 Issue: 1 Pages: 6750-6750

    • DOI

      10.1038/ncomms7750

    • NAID

      120005595832

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reducing DNA methylation suppresses colon carcinogenesis by inducing tumor cell differentiation. Carcinogenesis.2015

    • Author(s)
      Hatano Y, Semi K, Hashimoto K, Lee MS, Hirata A, Tomita H, Kuno T, Takamatsu M, Aoki K, Taketo MM, Kim YJ, Hara A, Yamada Y.
    • Journal Title

      Carcinogenesis

      Volume: 36 Issue: 7 Pages: 719-29

    • DOI

      10.1093/carcin/bgv060

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] In situ differentiation of CD8αα T cells from CD4 T cells in peripheral lymphoid tissues2012

    • Author(s)
      Nambu Y., Hayashi T., Jang KJ, Aoki K., Mano H., Nakano K., Osato M., Takabashi K., Itoh K., Teramukai S., Komon T., Fujita J., Ito Y., Shimizu
    • Journal Title

      Scientific Reports

      Volume: 2 Issue: 1 Pages: 930-930

    • DOI

      10.1038/srep00642

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Enhanced intestinal mucosal barrier function by homeoprotein CDX2 through autophagy activation2016

    • Author(s)
      Aoki K., (1/12) et al.
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-12-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] nhanced intestinal mucosal barrier function by homeoprotein CDX2 through autophagy activation2016

    • Author(s)
      Nakaya M and Aoki K
    • Organizer
      第45回日本免疫学会
    • Place of Presentation
      沖縄コンベンションセンター(沖縄県宜野湾市)
    • Year and Date
      2016-12-05
    • Related Report
      2016 Annual Research Report
  • [Presentation] Suppression of intestinal cancer stemness and malignant progression by intestine-specific homeoproteins CDX1 and CDX22016

    • Author(s)
      Hori K and Aoki K (9/9) et al.
    • Organizer
      第39回日本分子生物学会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Blocking intestinal cancer stemness and malignant progression by intestine-specific homeoproteins CDX1 and CDX22016

    • Author(s)
      Aoki K and Hori K
    • Organizer
      第3回北陸エピジェネティクス
    • Place of Presentation
      AOSSA(福井県福井市)
    • Year and Date
      2016-11-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] Suppression of intestinal cancer stemness and malignant progression by intestine-specific homeoproteins CDX1 and CDX22016

    • Author(s)
      Aoki K
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Suppression of intestinal cancer stemness and malignant progression by intestine-specific homeoproteins CDX1 and CDX22015

    • Author(s)
      Koji Aoki, Kazuya Hori, Takanori Goi, Akio Yamaguchi, Makoto M. Taketo and Manabu Sugai
    • Organizer
      日本癌学会シンポジウム がん幹細胞・微小環境・分子標的
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2015-01-21 – 2015-01-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] Roles of intestine-specific homeoprotein CDX2 in the intestinal epithelial barrier2014

    • Author(s)
      Koji Aoki and Mako Nakaya
    • Organizer
      日本免疫学会
    • Place of Presentation
      石川県立音楽堂交流ホール
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Roles of intestine-specific homeoprotein CDX2 in the intestinal epithelial barrier2014

    • Author(s)
      Koji Aoki, Shun-ichiro Iemura, Katsuya Okawa, Isei Tanida, Taira Kobayashi, Hitomi Mimuro, Sanada Takahito, Chihiro Sasakawa, Tohru Natume, Makoto M Taketo and Manabu Sugai
    • Organizer
      日本分子生物学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Book] Chronic inflammation: Elucidation and Control of the mechanisms2016

    • Author(s)
      Aoki K* and Sugai M
    • Total Pages
      14
    • Publisher
      Springer Press
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] ATG7変異体を用いたオートファジーの抑制方法2012

    • Inventor(s)
      青木耕史、谷田似誠
    • Industrial Property Rights Holder
      青木耕史、谷田似誠
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-12-21
    • Acquisition Date
      2016-12-09
    • Related Report
      2016 Annual Research Report
  • [Patent(Industrial Property Rights)] ATG7変異株を用いたオートファジーの制御方法2012

    • Inventor(s)
      青木耕史、谷田以誠
    • Industrial Property Rights Holder
      福井大学
    • Industrial Property Number
      2012-280082
    • Filing Date
      2012-12-21
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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