2013 Fiscal Year Final Research Report
Analysis for the role of mTORC1 in the self-renew of leukemia stem cell
| Project/Area Number |
24790967
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Kanazawa University |
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Principal Investigator |
HOSHII Takayuki 金沢大学, がん進展制御研究所, 助教 (20464042)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | mTOR / 自己複製 |
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| Research Abstract |
Mammalian target of rapamycin (mTOR) is identified as a target protein of immunosuppressive agent rapamycin, and this protein kinase is known to form two different complexes, named mTORC1 and mTORC2. In past years, we reported that mTORC1 inactivation, by Raptor deficiency, apparently suppressed the acute myeloid leukemia (AML) cell propagation and differentiation, but some AML cells with stem cell properties survived and proliferated in vivo. To identify the molecular mechanisms to maintain the stem cell like population after mTORC1 inactivation, we performed a quantitative phosphoproteomics study and cell surface proteomics study. We identified mTORC1 downstream candidate genes from phosphoproteomics study, and AML-stem cell associated cell surface molecules from cell surface protemics study. The findings will provide the new therapeutic targets for drug-resistant leukemia therapy.
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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 cells2014
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 KI, Matsuda S, Hirao A
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Journal Title
Proc Natl Acad Sci U S A
Volume: 111(10)
Pages: 3805-10
DOI
Peer Reviewed
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[Journal Article] Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy2013
Author(s)
Ichimura Y, Waguri S, Sou Y, Kageyama S, Hasegawa J, Ishimura R, Saito T, Yang Y, Kouno T, Fukutomi T, Hoshii T, Hirao A, Takagi K, Mizushima T, Motohashi H, Lee MS, Yoshimori T, Tanaka K, Yamamoto M, Komatsu M
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Journal Title
Mol Cell
Volume: 51(5)
Pages: 618-31
DOI
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 MA, Katano M, Soga T, Nakanuma Y, Okuda A, Hirao A
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Journal Title
Am J Pathol
Volume: 183(2)
Pages: 592-603
DOI
Peer Reviewed
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[Journal Article] Nucleostemin in injury-induced liver regeneration2012
Author(s)
Shugo H, Ooshio T, Naito M, Naka K, Hoshii T, Tadokoro Y, Muraguchi T, Tamase A, Uema N, Yamashita T, Nakamoto Y, Suda T, Kaneko S, Hirao A
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Journal Title
Stem Cells Dev
Volume: 21(16)
Pages: 3044-54
DOI
Peer Reviewed
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[Journal Article] PI3K-Akt-mTORC1-S6K1/2 axis controls Th17 differentiation by regulating Gfi-1 expression and nuclear translocation of ROR<gamma>2012
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
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Journal Title
Cell Reports
Volume: 1(4)
Pages: 360-373
DOI
Peer Reviewed
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[Presentation] mTORC1 inactivation prevents and eradicates acute lymphoblastic T-cell leukemia2013
Author(s)
Takayuki Hoshii, Atuo Kasada, Tomoki Hatakeyama, Masashi Ohtani, Yuko Tadokoro, Kazuhito Naka, Tsuneo Ikenoue, Tomokatsu Ikawa, Hiroshi Kawamoto, Asushi Iwama, Kimi Araki, Ken-ichi Yamamura, Satoshi Matsuda, Atsushi Hirao
Organizer
2013 ASH annual meeting and exposition, New Orleans
Place of Presentation
LA (USA)
Year and Date
20131207-11
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