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The molecular mechanism of senescence-associated prolongation of inflammatory signaling and its effect on cancer micro-environments.

Research Project

Project/Area Number 23300343
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Carcinogenesis
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

OHTANI Naoko  公益財団法人がん研究会, がん研究所, 主任研究員 (50275195)

Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥21,970,000 (Direct Cost: ¥16,900,000、Indirect Cost: ¥5,070,000)
Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2011: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Keywords細胞老化 / 炎症性サイトカイン / がん微小環境 / 炎症とがん / 癌微小環境 / 肝がん / 肥満
Research Abstract

Cellular senescence is an irreversible cell proliferation arrest provoked by oncogenic impulse such as oncogene activation that creates harmful DNA damage, and is recognized as an important fail-safe mechanism. Recently, it has been reported that senescent cells produce various types of secretory proteins including inflammatory cytokines and chemokines. In this study, we investigated whether this senescence-associated secretory proteins promote cancer progression. We found that senescent hepatic stellate cells (HSCs) form cancer micro-environment in obesity-induced hepatocellular carcinoma tissue. Moreover, we clarified the mechanism of how HSCs senesce and what signal is involved in the production of secretory proteins.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (39 results)

All 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 7 results) Presentation (21 results) (of which Invited: 6 results) Remarks (3 results)

  • [Journal Article] Crosstalk between RB-pathway and AKT signaling forms a Quiescence-Senescence switch2014

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

      Cell Reports 10

      Volume: 7 Pages: 194-207

    • Related Report
      2013 Final Research Report
  • [Journal Article] Crosstalk between the RB-pathway and AKT signaling forms a Quiescence-Senescence switch.2014

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

      Cell Reports

      Volume: 7 Pages: 194-207

    • DOI

      10.1016/j.celrep.2014.03.006

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Roles and mechanisms of cellular senescence in regulation of tissue homeostasis2013

    • Author(s)
      Ohtani N and Hara E
    • Journal Title

      Cancer Science

      Volume: 104 Pages: 525-30

    • Related Report
      2013 Final Research Report
  • [Journal Article] Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome2013

    • Author(s)
      Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, Honda K, Ishikawa Y, Hara E, Ohtani N
    • Journal Title

      Nature

      Volume: 499 Pages: 97-101

    • Related Report
      2013 Final Research Report
  • [Journal Article] Antitumor Impact of p14ARF on Gefitinib-Resistant Non-Small Cell Lung Cancers2013

    • Author(s)
      Saito K, Takigawa N, Ohtani N, Iioka H, Tomita Y, Ueda R, Fukuoka J, Kuwahara K, Ichihara E, Kiura K, Kondo E
    • Journal Title

      Mol Cancer Ther

      Volume: 12 Pages: 1616-28

    • Related Report
      2013 Final Research Report
  • [Journal Article] Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome.2013

    • Author(s)
      Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K,
    • Journal Title

      Nature

      Volume: 499 Pages: 97-101

    • DOI

      doi: 10.1038/nature12347

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor Impact of p14ARF on Gefitinib-Resistant Non-Small Cell Lung Cancers.2013

    • Author(s)
      Saito K, Takigawa N, Ohtani N, Iioka H, Tomita Y, Ueda R, Fukuoka J, Kuwahara K, Ichihara E, Kiura K, Kondo E.
    • Journal Title

      Molecule Cancer Therapeutics

      Volume: 12 Pages: 1616-1628

    • DOI

      doi: 10.1158/1535-7163.MCT-12-1239

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞老化による発がん制御-細胞老化の功罪-2013

    • Author(s)
      佐藤正大、大谷直子、原 英二
    • Journal Title

      実験医学

      Volume: 31 Pages: 733-738

    • Related Report
      2013 Annual Research Report
  • [Journal Article] マイクロバイオームとがん2013

    • Author(s)
      大谷直子、原 英二
    • Journal Title

      医学のあゆみ

      Volume: 246 Pages: 1095-1101

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Ohtani N, Hara E.2013

    • Author(s)
      Roles and mechanisms of cellular senescence in regulation of tissue homeostasis.
    • Journal Title

      Cancer Science

      Volume: 104 Pages: 525-530

    • DOI

      doi: 10.1111/cas.12118.

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 大谷直子2013

    • Author(s)
      細胞老化と慢性炎症
    • Journal Title

      アンチエイジング

      Volume: 9 Pages: 40-46

    • Related Report
      2012 Annual Research Report
  • [Journal Article] Cellular senescence: a double-edged sword in the fight against cancer.2012

    • Author(s)
      Ohtani N, Takahashi A, Mann DJ, Hara E.
    • Journal Title

      Experimental Dermatology

      Volume: 21, supplement 1 Pages: 1-4

    • DOI

      doi: 10.1111/j.1600-0625.2012.01493.x.

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA Damage Signaling Triggers Degradation of Histone Methyltransferases through APC/C^<Cdh1> in Senescent Cells2012

    • Author(s)
      Takahashi A, Imai Y, Yamakoshi K, Kuninaka S, Ohtani N, Yoshimoto S, Hori S, Tachibana M, Anderton E, Takeuchi T, Shinkai Y, Peters G, Saya H, Hara E
    • Journal Title

      Molecular Cell

      Volume: Vol 45 Pages: 123-131

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular senescence : a double-edged sword in the fight against cancer2012

    • Author(s)
      Ohtani N, Takahashi A, Mann D.J., Hara E
    • Journal Title

      Experimental Dermatology

      Volume: (in press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞老化のがん抑制と発癌促進における役割2011

    • Author(s)
      大谷直子、原英二
    • Journal Title

      実験医学

      Volume: vol.29 Pages: 85-91

    • Related Report
      2011 Annual Research Report
  • [Presentation] 細胞老化・SASPによる発がん-肥満により増加する腸内細菌の代謝産物DCAは肝がんを促進する-2014

    • Author(s)
      大谷直子
    • Organizer
      第23回日本小児胆汁酸研究会
    • Year and Date
      2014-02-15
    • Related Report
      2013 Final Research Report
  • [Presentation] 肥満に伴い増加する腸内細菌の代謝産物デオキシコール酸によるSASPを介した肝がん促進作用2014

    • Author(s)
      大谷直子, 吉本 真, 羅 智文, 原 英二
    • Organizer
      第47回日本無菌生物ノートバイオロジー学会総会 シンポジウム
    • Year and Date
      2014-01-31
    • Related Report
      2013 Final Research Report
  • [Presentation] 細胞老化による炎症とがん -肥満に伴い増加する腸内細菌の代謝産物による肝がん促進作用-2013

    • Author(s)
      大谷直子, 吉本 真, 羅 智文, 原 英二
    • Organizer
      第36回日本分子生物学会年会 ワークショップ 「生老病死」の分子生物学の最前線
    • Year and Date
      2013-12-03
    • Related Report
      2013 Final Research Report
  • [Presentation] 肥満により増加する腸内細菌の代謝産物が肝がんを促進する2013

    • Author(s)
      大谷直子
    • Organizer
      第41回臨床免疫学会総会 シンポジウム
    • Year and Date
      2013-11-28
    • Related Report
      2013 Final Research Report
  • [Presentation] 肥満により増加する腸内細菌の代謝産物DCAは肝癌発症を促進する2013

    • Author(s)
      大谷直子
    • Organizer
      第1回がんと代謝研究会
    • Year and Date
      2013-10-30
    • Related Report
      2013 Final Research Report
  • [Presentation] The role of cellular senescence in obesity-associated hepatic carcinogenesis2013

    • Author(s)
      Ohtani N, Hara E
    • Organizer
      第72回日本癌学会総会 シンポジウム Animal models in cancer research
    • Year and Date
      2013-10-05
    • Related Report
      2013 Final Research Report
  • [Presentation] 細胞老化による炎症とがん-肥満により増加する腸内細菌の代謝産物が肝がんを促進する-2013

    • Author(s)
      大谷直子
    • Organizer
      第45回北陸実験動物研究会
    • Year and Date
      2013-09-14
    • Related Report
      2013 Final Research Report
  • [Presentation] Obesity-induced gut microbial metabolite promotes liver cancer via senescence secretome2013

    • Author(s)
      Naoko Ohtani, Shin Yoshimoto, Tze Mun Loo, Hiroaki Kanda, Seidai Sato, Yuichi Ishikawa and Eiji Hara
    • Organizer
      Welcome Trust scientific conference. Cell Senescence in Cancer and Aging
    • Year and Date
      2013-07-22
    • Related Report
      2013 Final Research Report
  • [Presentation] 細胞老化の二面性 -がん抑制機構SASP-2013

    • Author(s)
      大谷直子
    • Organizer
      第65回日本細胞生物学会大会 シンポジウム 老化の分子機構
    • Year and Date
      2013-06-21
    • Related Report
      2013 Final Research Report
  • [Presentation] Senescence-associated inflammatory secretome and cancer development2013

    • Author(s)
      Naoko Ohtani
    • Organizer
      JST-CREST International Symposium "Frontiers in Immunology and Inflammation"
    • Year and Date
      2013-02-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Cellular senescence-associated inflammation and cancer2012

    • Author(s)
      Naoko Ohtani
    • Organizer
      2nd Japanese-French Cancer Workshop
    • Year and Date
      2012-11-29
    • Related Report
      2013 Final Research Report
  • [Presentation] Senescence-Associated Secretory Phenotypes (SASPs) Promote Obesity Associated Hepatocarcinogenesis2012

    • Author(s)
      Naoko Ohtani
    • Organizer
      Keystone Symposia "Aging and Dideases of Aging"
    • Year and Date
      2012-10-25
    • Related Report
      2013 Final Research Report
  • [Presentation] Senescence-associated secretory phenotype (SASP) in fatty-liver based hepatic cancer2011

    • Author(s)
      Naoko Ohtani, Shin Yoshimoto, Eiji Hara
    • Organizer
      第34回日本分子生物学会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] The role of cellular senescence in obesity-associated hepatic carcinogenesis

    • Author(s)
      Naoko Ohtani and Eiji Hara
    • Organizer
      第72回日本癌学会総会シンポジウム
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 肥満により増加する腸内細菌の代謝産物DCAは肝がん発症を促進する

    • Author(s)
      大谷直子
    • Organizer
      第1回がんと代謝研究会 特別講演
    • Place of Presentation
      鶴岡
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 肥満により増加する腸内細菌の代謝産物が肝がんを促進する

    • Author(s)
      大谷直子
    • Organizer
      第41回日本臨床免疫学会総会シンポジウム
    • Place of Presentation
      下関
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 細胞老化による炎症とがん-肥満に伴い増加する腸内細菌の代謝産物による肝がん促進作用-

    • Author(s)
      大谷直子
    • Organizer
      第36回分子生物学会年会 ワークショップ
    • Place of Presentation
      神戸
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Senescence-Associated Secretory Phenotypes(SASPs) Promote Obesity Associated Hepatocarcinogenesis

    • Author(s)
      Naoko Ohtani
    • Organizer
      Keystone Symposia〝Aging and Dideases of Aging″
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2012 Annual Research Report
  • [Presentation] Cellular senescence-associated inflammation and cancer

    • Author(s)
      Naoko Ohtani
    • Organizer
      2nd Japanese-French Cancer Workshop
    • Place of Presentation
      Naruto, Japan
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Senescence-associated inflammatory secretome and cancer development

    • Author(s)
      Naoko Ohtani
    • Organizer
      JST-CREST International Symposium 〝Frontiers in Immunology and Inflammation″
    • Place of Presentation
      Tokyo, Japan
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Induction of cellular senescence in obesity-associated hepatic carcinogenesis

    • Author(s)
      Shin Yoshimoto, Tze Mun Loo, Hiroaki Kanda, Seidai Sato, Yuichi Ishikawa, Eiji Hara & Naoko Ohtani
    • Organizer
      Keystone Symposia〝The Role of Inflammation during Carcinogenesis″
    • Place of Presentation
      Dublin, Ireland
    • Related Report
      2012 Annual Research Report
  • [Remarks] 肥満に伴う腸内細菌の変化が肝がんの発症を促進する

    • URL

      http://www.jfcr.or.jp/laboratory/pickup/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 肥満に伴う腸内細菌の変化が肝がんの発症を促進する

    • URL

      http://www.jst.go.jp/pr/announce/20130627-2/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] Gut microbes spur liver cancer in obese mice

    • URL

      http://www.jst.go.jp/pr/announce/20130627-2/index.html

    • Related Report
      2013 Annual Research Report

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Published: 2011-04-06   Modified: 2025-11-18  

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