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Understanding of the anti-apoptotic mechanisms in senescent cells

Research Project

Project/Area Number 24650625
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

HARA Eiji  公益財団法人がん研究会, がん研究所がん生物部, 部長 (80263268)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords癌 / 遺伝子 / シグナル伝達 / 老化 / 発現制御 / 細胞老化 / アポトーシス / 発がん / 国際情報交換 / 発癌
Outline of Final Research Achievements

We have tried to identify a promising molecular target that can be used to design interventions to promote apoptosis in senescent cells. By screening of a low molecular weight compound library, we found that a series of chemical inhibitors against the same histone modifying enzyme can provoke apoptosis in senescent, but not in non-senescent, human diploid fibroblasts. Similar results were also observed when we used several other human cell types, suggesting that this histone modifying enzyme plays a key role in preventing apoptosis in senescent human cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (22 results)

All 2015 2014 2013 2012

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (12 results) (of which Invited: 12 results)

  • [Journal Article] In vivo imaging models of bone and brain metastases and pleural carcinomatosis with a novel human EML4-ALK lung cancer cell line.2015

    • Author(s)
      Nanjo S, Yano S, et al.
    • Journal Title

      Cancer Sci

      Volume: 106 Issue: 3 Pages: 244-52

    • DOI

      10.1111/cas.12600

    • NAID

      120005830611

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evidence for a CDK4-dependent checkpoint in a conditional model of cellular senescence.2015

    • Author(s)
      Brookes S, Gagrica S, Sanij E, Rowe J, Gregory FJ, Hara E, and *Peters G.
    • Journal Title

      Cell Cycle

      Volume: 14 Issue: 8 Pages: 1164-1173

    • DOI

      10.1080/15384101.2015.1010866

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysregulation of the Bmi-1/p16Ink4a pathway provokes an aging-associated decline of submandibular gland function.2015

    • Author(s)
      Yamakoshi K, Katano S, Iida M, Kimura H, Okuma A, Ikemoto-Uezumi M, Ohtani N, Hara E, Maruyama M.
    • Journal Title

      Aging Cell

      Volume: - Issue: 4 Pages: 1-9

    • DOI

      10.1111/acel.12337

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ablation of the p16INK4a tumour suppressor reverses ageing phenotypes of klotho mice2015

    • Author(s)
      Seidai Sato, Yuka Kawamata, Akiko Takahashi, Yoshinori Imai, Aki Hanyu, Atsushi Okuma, Masaki Takasugi, Kimi Yamakoshi, Hiroyuki Sorimachi, Hiroaki Kanda, Yuichi Ishikawa, Saburo Sone, Yasuhiko Nishioka, Naoko Ohtani and Eiji Hara
    • Journal Title

      Nature communications

      Volume: 6 Issue: 1 Pages: 7035-7035

    • DOI

      10.1038/ncomms8035

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Crosstalk between the RB-pathway and AKT signalling forms a Quiescence-Senescence switch.2014

    • Author(s)
      Imai, Y., Takahashi, A., Hanyuu, A., Hori, S., Sato, S., Naka, K., Hirao, A., Ohtani, N., Hara, E.
    • Journal Title

      Cell Reports

      Volume: 7 Issue: 1 Pages: 194-207

    • DOI

      10.1016/j.celrep.2014.03.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Obesity and Cancer: a gut microbial connection2014

    • Author(s)
      Ohtani, N.
    • Journal Title

      Cancer Research

      Volume: 74 Issue: 7 Pages: 1885-11889

    • DOI

      10.1158/0008-5472.can-13-3501

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Necessary and sufficient role for a mitosis skip in senescence induction.2014

    • Author(s)
      Johmura Y, Shimada M, Misaki T, Naiki-Ito A, Miyoshi H, Motoyama N, Ohtani N, Hara E, Nakamura M, Morita A, Takahashi S, Nakanishi M.
    • Journal Title

      Mol.Cell

      Volume: 55 Issue: 1 Pages: 73-84

    • DOI

      10.1016/j.molcel.2014.05.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.2014

    • Author(s)
      Demaria, M., Ohtani, N., Youssef, S.A., Rodier, F., Toussaint, W., Mitchell, J.R., Laberge, R.M., Vijg, J., Van Steeg, H., Dollé, M.E.T., Hoeijmakers, J.H.J., de Bruin, A., Hara, E.., Campisi, J.
    • Journal Title

      Developmental Cell

      Volume: 31 Issue: 6 Pages: 722-733

    • DOI

      10.1016/j.devcel.2014.11.012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome2013

    • Author(s)
      Yoshimoto, S.
    • Journal Title

      Nature

      Volume: 499 Issue: 7456 Pages: 97-101

    • DOI

      10.1038/nature12347

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protein Kinase A Determines Timing of Early Differentiation through Epigenetic Regulation with G9a2012

    • Author(s)
      Yamamizu K, Fujihara M, Tachibana M, Katayama S, Takahashi A, Hara E, Imai H, Shinkai Y, and Yamashita JK
    • Journal Title

      Cell Stem Cell

      Volume: 10 Issue: 6 Pages: 759-770

    • DOI

      10.1016/j.stem.2012.02.022

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 細胞老化の発がん制御における役割2015

    • Author(s)
      原 英二
    • Organizer
      ヒューマンサイエンス総合研究セミナー
    • Place of Presentation
      東京
    • Year and Date
      2015-01-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The roles of cellular senescence in aging and cancer2014

    • Author(s)
      Akiko Takahashi & Eiji Hara
    • Organizer
      日本分子生物学会シンポジウム
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞老化による発がん制御2014

    • Author(s)
      原 英二
    • Organizer
      肺リモデリング研究会
    • Place of Presentation
      東京
    • Year and Date
      2014-11-08
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞老化反応の生体内イメージング2014

    • Author(s)
      大熊敦史、大谷直子、山越貴水、原 英二
    • Organizer
      日本生化学会シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2014-10-15 – 2014-10-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Crosstalk between the Rb-pathway and AKT signaling forms a Quiescence- Senescence switch2014

    • Author(s)
      Eiji Hara
    • Organizer
      日本癌学会コアシンポジウム
    • Place of Presentation
      神奈川県横浜市
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞老化と癌:細胞老化の功罪2014

    • Author(s)
      原 英二
    • Organizer
      高遠・分子細胞生物学シンポジウム
    • Place of Presentation
      長野県伊那市
    • Year and Date
      2014-08-28 – 2014-08-29
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞老化と炎症2014

    • Author(s)
      原 英二
    • Organizer
      日本動脈硬化学会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-10 – 2014-07-12
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞老化と炎症2014

    • Author(s)
      原 英二
    • Organizer
      炎症・再生医学会シンポジウム
    • Place of Presentation
      沖縄県名護市
    • Year and Date
      2014-07-01 – 2014-07-03
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The roles and mechanisms of cellular senescence2014

    • Author(s)
      Eiji Hara
    • Organizer
      日本基礎老化学会国際シンポジウム
    • Place of Presentation
      愛知県大府市
    • Year and Date
      2014-06-26 – 2014-06-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 細胞老化と発癌2014

    • Author(s)
      原 英二
    • Organizer
      日本臨床分子医学会 シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2014-04-12 – 2014-04-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome2013

    • Author(s)
      Hara, E.
    • Organizer
      17th International Symposium on Cell of the Hepatic Sinusoid.
    • Place of Presentation
      大阪市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] The roles of cellular senescence in cancer and aging.2012

    • Author(s)
      原 英二
    • Organizer
      日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
    • Invited

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Published: 2013-05-31   Modified: 2019-07-29  

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