Role of nutrient signals in stem cell regulation in tumors
| Project/Area Number |
24240119
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Kanazawa University |
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Principal Investigator |
HIRAO Atsushi 金沢大学, がん進展制御研究所, 教授 (90343350)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| 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)
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| Keywords | 白血病 / mTOR / 白血病幹細胞 / 栄養シグナル |
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| 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.
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Report
(4 results)
Research Products
(24 results)
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[Journal Article] Strong therapeutic potential of γ-secretase inhibitor MRK003 for CD44-high and CD133-low glioblastoma initiating cells.2015
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.
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Journal Title
J Neurooncol.
Volume: 121
Issue: 2
Pages: 239-50
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Biochem Biophys Res Commun.
Volume: 450
Issue: 1
Pages: 837-843
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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.
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Journal Title
Cell Reports
Volume: 7
Issue: 1
Pages: 194-207
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[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
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 111
Issue: 10
Pages: 3805-3810
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Am. J. Pathol.
Volume: 183
Issue: 2
Pages: 592-603
DOI
Related Report
Peer Reviewed
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