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Defense mechanisms against aging and cancer: lessons from the naked mole rats

Research Project

Project/Area Number 26640078
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionOsaka University

Principal Investigator

Okada Masato  大阪大学, 微生物病研究所, 教授 (10177058)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywordsがん / 老化 / ハダカデバネズミ / mTOR / がん化 / FoxO3
Outline of Final Research Achievements

The naked mole rat (NMR) has recently attracted attention for its longevity and resistance to cancer. This study aimed to elucidate the molecular basis for these remarkable features. We first analyzed the mTOR signaling pathway, which had been implicated in aging and caner, and found that the transcription factor FoxO3a is constitutively activated and localized to the nucleus in NMR cells. We also observed that knockdown of FoxO3a suppressed the contact inhibition of cell growth in NMR cells, while the expression of active form of FoxO3a inhibited cell growth in mouse cells. These findings demonstrate that NMR has a unique system for the regulation of FoxO3a and shed new lights on the role of FoxO3a as a regulatory point of longevity and resistance to cancer.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (11 results)

All 2015 2014

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (6 results) (of which Invited: 2 results)

  • [Journal Article] Fer tyrosine kinase oligomer mediates and amplifies Src-induced tumor progression2015

    • Author(s)
      Oneyama C, Yoshikawa Y, Ninomiya Y, Iino T, Tsukita S, Okada M
    • Journal Title

      Oncogene

      Volume: 35 Issue: 4 Pages: 501

    • DOI

      10.1038/onc.2015.110

    • URL

      https://pure.teikyo.jp/en/publications/5eab79ca-728b-4573-acd2-1630ccbeab92

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] mLST8 promotes mTOR-mediated tumor progression.2015

    • Author(s)
      Kakumoto K, Ikeda J, Okada M, Morii E, Oneyama C
    • Journal Title

      PLos One

      Volume: 0 Pages: 0-0

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] c-Src-induced activation of ceramide metabolism impairs membrane microdomains and promotes malignant progression by facilitating the translocation of c-Src to focal adhesions2014

    • Author(s)
      Kajiwara K, Yamada T, Bamba T, Fukusaki E, Imamoto F, Okada M, Oneyama C.
    • Journal Title

      Biochem J.

      Volume: 458(1) Issue: 1 Pages: 81-93

    • DOI

      10.1042/bj20130527

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] p18/LAMTOR1 : a late endosome/lysosome-specific anchor protein for the mTORC1/MAPK signaling pathway2014

    • Author(s)
      Nada S, Mori S, Takahashi Y, Okada M.
    • Journal Title

      Methods Enzymol

      Volume: 535 Pages: 249-63

    • DOI

      10.1016/b978-0-12-397925-4.00015-8

    • ISBN
      9780123979254
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The mTOR pathway controls cell proliferation by regulating the FoxO3a transcription factor via SGK1 kinase2014

    • Author(s)
      Mori S, Nada S, Kimura H, Tajima S, Takahashi Y, Kitamura A, Oneyama C, Okada M.
    • Journal Title

      PLos ONE

      Volume: 9(2) Issue: 2 Pages: e88891-e88891

    • DOI

      10.1371/journal.pone.0088891

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] マウス表皮におけるmTORC1シグナルの機能2015

    • Author(s)
      名田茂之、名田真理、長江(相馬)多恵子、北川真理、森俊介、高橋佑介、岡田雅人
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 老化と寿命におけるマウスおよびハダカデバネズミのFOXO3aの役割2015

    • Author(s)
      Junhyeong Kim、森俊介、名田茂之、三浦恭子、岡野栄之、岡田雅人
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-03
    • Related Report
      2015 Annual Research Report
  • [Presentation] mTORC1シグナルを制御するRagulatorの機能の分子基盤2015

    • Author(s)
      中井智和、名田茂之、中津海洋一、中山敬一、岡田雅人
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Function and molecular architecture of the lysosomal mTORC1 anchor: Ragulator2014

    • Author(s)
      Masato Okada, Ayaka Kitamura, Shunsuke Mori, Shigeyuki Nada, Tomokazu Nakai, Hirokazu Nakatsumi, Keiichi I. Nakayama
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] がん進展におけるEphexin family Rho GEFの機能解析2014

    • Author(s)
      小宮優、呑村優、名田茂之、小根山千歳、岡田雅人
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] マウス表皮の正常な発達はリソソーム膜アダプタータンパク質p18に依存している2014

    • Author(s)
      名田真里、名田 茂之、長江 多恵子、森 俊介、岡田 雅人
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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