Stem cell-specific phosphorylation of Smad3 for regulating self-renewal capacity in CML stem cells
| Project/Area Number |
26290038
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Hiroshima University (2015-2016)
Kanazawa University (2014) |
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Principal Investigator |
Naka Kazuhito 広島大学, 原爆放射線医科学研究所, 准教授 (70372688)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 慢性骨髄性白血病 / CML幹細胞 / チロシンキナーゼ阻害剤抵抗性 / 再発 / Smad3 / p38 MAPK / マウスモデル / 非臨床試験 / がん幹細胞 / TGF-beta / チロシンキナーゼ阻害剤 / がん微小環境 / 癌 / CML / TGF-β / 微小環境 |
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| Outline of Final Research Achievements |
Although the discovery of tyrosine kinase inhibitors (TKIs) has been improved prognosis of chronic myelogenous leukemia (CML) patients, CML stem cells are responsible for the relapse of CML disease following TKI therapy. In this study, we found that the stem cell-specific phosphorylation of Smad3 at Ser208 residue plays an essential role for the maintenance of self-renewal capacity in CML stem cells in vivo. In addition, p38MAPK regulated the phosphorylation of Smad3 at Ser208. Indeed, we demonstrated that the administration of an inhibitor targeting p38MAPK significantly delayed the disease relapse of CML-affected mice.
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells.2016
Author(s)
Naka K, Ishihara K, Jomen Y, Jin CH, Kim DH, Gu YK, Jeong ES, Li S, Krause DS, Kim DW, Bae E, Takihara Y, Hirao A, Oshima H, Oshima M, Ooshima A, Sheen YY, Kim SJ, Kim DK.
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Journal Title
Cancer Sci.
Volume: 107
Issue: 2
Pages: 140-148
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Dipeptide species regulate nutrient signalling essential for the maintenance of chronic myelogenous leukaemia stem cells.2015
Author(s)
Naka K, Jomen Y, Ishihara K, Kim J, Ishimoto T, Bae E, Mohney R, Stirdivant SM, Oshima H, Oshima M, Kim DW, Nakauchi H, Takihara Y, Kato Y, Ooshima A, Kim SJ.
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Journal Title
Nature Communication
Volume: 6
Issue: 1
Pages: 8039-8039
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Homozygous Deletions at 3p22, 5p14, 6q15, and 9p21 Result in Aberrant Expression of Tumor Suppressor Genes in Gastric Cancer.2015
Author(s)
Lee B., Yoon K.Y., Lee S.H., Kang J.M., Kim J.I., Shim S.H., Kim H.-M., Song S.H., Naka K., Kim A.K., Yang H.-K., Kim S.J.
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Journal Title
Genes, Chromosomes and Cancer.
Volume: 54
Issue: 3
Pages: 142-155
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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