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Role of dedifferentiation on cancer development

Research Project

Project/Area Number 15H04721
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionThe University of Tokyo (2017)
Kyoto University (2015-2016)

Principal Investigator

Yamada Yasuhiro  東京大学, 医科学研究所, 教授 (70313872)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywordsdedifferentiation / cancer / iPS cell / reprogramming / 脱分化 / 膵癌 / がん / iPS細胞 / 細胞初期化 / マウス / リプログラミング
Outline of Final Research Achievements

The faithful shutdown of the somatic program occurs in the early stage of reprogramming. Here, we examined the effect of in vivo reprogramming on Kras-induced cancer development. We show that the transient expression of reprogramming factors in pancreatic acinar cells results in the transient repression of acinar cell enhancers. Notably, the transient expression of reprogramming factors in Kras mutant mice is sufficient to induce the rapid formation of pancreatic ductal adenocarcinoma. These results underscore a crucial role of dedifferentiation-associated epigenetic regulations in the initiation of pancreatic cancers.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (16 results)

All 2017 2016 2015

All Journal Article (8 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 4 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 7 results,  Invited: 8 results)

  • [Journal Article] In vivo reprogramming for tissue regeneration and organismal rejuvenation2017

    • Author(s)
      Taguchi Jumpei、Yamada Yasuhiro
    • Journal Title

      Curr Opin Genet Dev.

      Volume: 46 Pages: 132-140

    • DOI

      10.1016/j.gde.2017.07.008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Unveiling the role of senescence-induced cellular plasticity.2017

    • Author(s)
      Taguchi J, *Yamada Y.
    • Journal Title

      Cell Stem Cell.

      Volume: 20(3) Issue: 3 Pages: 293-294

    • DOI

      10.1016/j.stem.2017.02.001

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular context-dependent consequences of Apc mutations on gene regulation and cellular behavior.2017

    • Author(s)
      Hashimoto K, Yamada Y, Semi K, Yagi M, Tanaka A, Itakura F, Aoki H, Kunisada T, Woltjen K, Haga H, Sakai Y, Yamamoto T, *Yamada Y.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 114 Issue: 4 Pages: 758-763

    • DOI

      10.1073/pnas.1614197114

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation2017

    • Author(s)
      Yagi M, Kishigami S, Tanaka A, Semi K, Mizutani E, Wakayama S, Wakayama T, Yamamoto T, Yamada Y.
    • Journal Title

      Nature

      Volume: 548 Issue: 7666 Pages: 224-227

    • DOI

      10.1038/nature23286

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cellular reprogramming technology for dissecting cancer epigenome in vivo2017

    • Author(s)
      Ito Kenji、Yamada Yasuhiro
    • Journal Title

      Epigenomics

      Volume: 9 Issue: 7 Pages: 997-1011

    • DOI

      10.2217/epi-2017-0018

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] EWS-FLI1-induced osteosarcoma model unveiled a crucial role of impaired osteogenic differentiation on osteosarcoma development.2016

    • Author(s)
      Komura S, Semi K, Itakura F, Shibata H, Ohno T, Hotta A, Woltjen K, Yamamoto T, Akiyama H, Yamada Y.
    • Journal Title

      Stem Cell Reports

      Volume: 6(4) Issue: 4 Pages: 592-606

    • DOI

      10.1016/j.stemcr.2016.02.009

    • NAID

      120005756300

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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] Induced pluripotent stem cell technology for dissecting the cancer epigenome.2015

    • Author(s)
      Semi K, Yamada Y.
    • Journal Title

      Cancer Sci

      Volume: 106 Issue: 10 Pages: 1251-6

    • DOI

      10.1111/cas.12758

    • NAID

      120005767027

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Dissecfing cancer biology with reprogramming technology.2017

    • Author(s)
      Yasuhiro Yamada
    • Organizer
      IHEC 2017 Science Days
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dissecting cancer biology with iPS cell technology.2017

    • Author(s)
      Yasuhiro Yamada
    • Organizer
      CSCB Seminar Series
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Dissecting Cancer Biology with iPSC Technology2016

    • Author(s)
      山田泰広
    • Organizer
      Nature Conference
    • Place of Presentation
      サンディエゴ 米国
    • Year and Date
      2016-02-21
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dissecting cancer epigenome with iPS cell technology2016

    • Author(s)
      山田泰広
    • Organizer
      10th AACR-JCA Joint Conference
    • Place of Presentation
      ハワイ 米国
    • Year and Date
      2016-02-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] DISSECTING CANCER BIOLOGY WITH iPSC TECHNOLOGY2016

    • Author(s)
      Yamada Y
    • Organizer
      The 41st NAITO Conference
    • Place of Presentation
      札幌
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Dissecting the cancer biology with iPS cell technology2016

    • Author(s)
      Yamada Y
    • Organizer
      The 9th Guangzhou International Conference on Stem Cell and Regenerative Medicine
    • Place of Presentation
      Guangzhou
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS cell technology for dissecting the cancer epigenome2015

    • Author(s)
      山田泰広
    • Organizer
      10th Asian Epigenomics Meeting 2015
    • Place of Presentation
      ソウル 韓国
    • Year and Date
      2015-09-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 1.Cancer Cell Reprogramming Unveils Stable Maintenance of Cancer Cell Identity through Key Oncogenic Signals2015

    • Author(s)
      山田泰広
    • Organizer
      ISSCR Annual Meeting 2015
    • Place of Presentation
      ストックホルム スェーデン
    • Year and Date
      2015-06-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2015-04-16   Modified: 2019-03-29  

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