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Role of nutrient signals in stem cell regulation in tumors

Research Project

Project/Area Number 24240119
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Tumor biology
Research InstitutionKanazawa University

Principal Investigator

HIRAO Atsushi  金沢大学, がん進展制御研究所, 教授 (90343350)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥46,800,000 (Direct Cost: ¥36,000,000、Indirect Cost: ¥10,800,000)
Fiscal Year 2014: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2013: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000)
Fiscal Year 2012: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Keywords白血病 / mTOR / 白血病幹細胞 / 栄養シグナル
Outline of Final Research Achievements

mTOR is an evolutionarily conserved kinase that plays a critical role in sensing and responding to nutrients. In this study, we investigated roles of mTOR complex 1 (mTORC1) in hematopoiesis and leukemogenesis. In an acute myeloid leukemia model, deficiency of Raptor, an essential component of mTORC1, significantly suppressed leukemia progression by causing apoptosis of differentiated cells, but did not affect self-renewal of leukemia stem cells. In contrast, we found that mTORC1 plays a critical role in the development of both early T-cell progenitors and leukemia. Thus, understanding the cell-context-dependent role of mTORC1 illustrates the potential importance of mTOR signals as therapeutic targets.

Report

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

    (24 results)

All 2015 2014 2013 2012

All Journal Article (14 results) (of which Peer Reviewed: 14 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (10 results) (of which Invited: 10 results)

  • [Journal Article] Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells2015

    • Author(s)
      Tanaka S, Nakada M, Yamada D, Nakano I, Todo T, Ino Y, Hoshii T, Tadokoro Y, Ohta K, Ali MA, Hayashi Y, Hamada J, Hirao A.
    • Journal Title

      J Neurooncol.

      Volume: 121 Issue: 2 Pages: 239

    • DOI

      10.1007/s11060-014-1630-z

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pleiotropic roles of mTOR complexes in haemato-lymphopoiesis and leukemogenesis.2014

    • Author(s)
      Hoshii T, Matsuda S, Hirao A.
    • Journal Title

      J Biochem.

      Volume: 156 Issue: 2 Pages: 73-83

    • DOI

      10.1093/jb/mvu037

    • NAID

      40020155036

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of a murine leukaemia stem cell gene signature based on nucleostemin promoter activity with prognosis of acute myeloid leukaemia in patients.2014

    • Author(s)
      Ali MA, Naka K, Yoshida A, Fuse K, Kasada A, Hoshii T, Tadokoro Y, Ueno M, Ohta K, Kobayashi M, Takahashi C, Hirao A.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 450 Issue: 1 Pages: 837-843

    • DOI

      10.1016/j.bbrc.2014.06.066

    • 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] Loss of Tsc1 accelerates malignant gliomagenesis when combined with oncogenic signals.2014

    • Author(s)
      Yamada D, Hoshii T, Tanaka S, Hegazy AM, Kobayashi M, Tadokoro Y, Ohta K, Ueno M, Ali MAE, Hirao A.
    • Journal Title

      J Biochem.

      Volume: 155 Issue: 4 Pages: 227-33

    • DOI

      10.1093/jb/mvt112

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Loss of mTOR complex 1 induces developmental blockage in early T-lymphopoiesis and eradicates T-cell acute lymphoblastic leukemia cells.2013

    • Author(s)
      Hoshii T, Kasada A, Hatakeyama T, Ohtani M, Tadokoro Y, Naka K, Ikenoue T, Ikawa T, Kawamoto H, Fehling HJ, Araki K, Yamamura K, Matsuda S, Hirao A
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 111 Issue: 10 Pages: 3805-3810

    • DOI

      10.1073/pnas.1320265111

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Abundant nucleostemin expression supports the undifferentiated properties of germ cell tumors2013

    • Author(s)
      Uema, N., Ooshio, T., Harada, K., Naito, M., Naka, K., Hoshii, T., Tadokoro, Y., Ohta, K., Ali, M.A., Katano, M., Soga, T., Nakanuma, Y., Okuda, A., Hirao, A.
    • Journal Title

      Am. J. Pathol.

      Volume: 183 Issue: 2 Pages: 592-603

    • DOI

      10.1016/j.ajpath.2013.04.018

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanistic/mammalian target protein of rapamycin signaling in hematopoietic stem cells and leukemia.2013

    • Author(s)
      Hirao A, Hoshii T.
    • Journal Title

      Cancer Sci.

      Volume: 104 Issue: 8 Pages: 977-82

    • DOI

      10.1111/cas.12189

    • NAID

      120005830607

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ablation of fbxw7 eliminates leukemia-initiating cells by preventing quiescence.2013

    • Author(s)
      Takeishi S
    • Journal Title

      Cancer Cell

      Volume: 23 Issue: 3 Pages: 347-361

    • DOI

      10.1016/j.ccr.2013.01.026

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of glycolysis by Pdk functions as a metabolic checkpoint for cell cycle quiescence in hematopoietic stem cells.2013

    • Author(s)
      Takubo K
    • Journal Title

      Cell Stem Cell

      Volume: 12 Issue: 1 Pages: 49-61

    • DOI

      10.1016/j.stem.2012.10.011

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mTORC1is essential for leukemia propagation but not stem cell self-renewal.2012

    • Author(s)
      Hoshii. T
    • Journal Title

      J Clin Invest.

      Volume: 122 Issue: 6 Pages: 2114-2129

    • DOI

      10.1172/jci62279

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nucleostemin in injury-induced liver regeneration.2012

    • Author(s)
      Shugo. H
    • Journal Title

      Stem cells Dev.

      Volume: 21 Issue: 16 Pages: 3044-3054

    • DOI

      10.1089/scd.2011.0725

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] mTORC1 in Intestinal CD11c+CD11b+Dendritic Cells Regulates Intestinal Homeostasis by Promoting IL-10 Production2012

    • Author(s)
      Ohtani M, Hoshii T, Fujii H, Koyasu S, Hirao A, Matsuda S.
    • Journal Title

      J Immunol

      Volume: 188 Issue: 10 Pages: 4736-40

    • DOI

      10.4049/jimmunol.1200069

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi-1 expression and nuclear translocation of RORγ2012

    • Author(s)
      Kurebayashi Y. Nagai S. Ikejiri A. Ohtani M. Ichiyama K. Baba Y. Yamada T. Egami S. Hoshii T. Hirao A. Matsuda S. Koyasu S.
    • Journal Title

      Cell Reports

      Volume: 1 Issue: 4 Pages: 360-373

    • DOI

      10.1016/j.celrep.2012.02.007

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Role of c-Kit signal modulation in the control of self-renewal and aging of hematopoietic stem cells.2015

    • Author(s)
      Hirao A
    • Organizer
      2015 US-Japan meeting on malignant hematopoiesis and stem cells
    • Place of Presentation
      米国
    • Year and Date
      2015-03-16 – 2015-03-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The signaling pathways for the determination of hematopoietic stem cell fate.2014

    • Author(s)
      平尾 敦
    • Organizer
      第76回日本血液学会学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The nutrient sensing signaling in the cancer stem cells.2014

    • Author(s)
      平尾 敦
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The nutrient sensing signaling pathways in the hematopoietic and leukemia stem cells.2014

    • Author(s)
      Hirao A
    • Organizer
      SNUCRI CANCER SYMPOSIUM
    • Place of Presentation
      韓国
    • Year and Date
      2014-04-16 – 2014-04-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The nutrient sensing signaling pathways in the hematopoietic stem cells and leukemia.2013

    • Author(s)
      Hirao A
    • Organizer
      SUCRI-KUCRI Joint Symposium
    • Place of Presentation
      Seoul National University (Korea)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] The nutrient sensing signaling pathways in the hematopoietic stem cells and leukemia.2013

    • Author(s)
      Hirao A
    • Organizer
      The 23th Hot Spring Harbor International Symposium
    • Place of Presentation
      Kyushu University(Fukuoka)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 栄養センサーシグナルと幹細胞制御2013

    • Author(s)
      平尾敦
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 栄養センサーシグナルとがん幹細胞2012

    • Author(s)
      平尾 敦
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      ロイトン札幌(札幌)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] The nutrient sensing signaling pathways in the hematopoietic stem cells and leukemia.2012

    • Author(s)
      Hirao A
    • Organizer
      New Frontiers of Metabolism Research in Biomedical Sciences
    • Place of Presentation
      東京大学(東京)
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] The nutrient sensing signaling pathways in cancer2012

    • Author(s)
      平尾 敦
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Related Report
      2012 Annual Research Report
    • Invited

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Published: 2013-05-15   Modified: 2019-07-29  

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