Inflammatory circuit that triggres malignant progression
Project/Area Number |
26640070
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Tumor biology
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Research Institution | Kanazawa University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
KITAJIMA Shunsuke 金沢大学, がん進展制御研究所, 教授 (90566465)
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Project Period (FY) |
2014-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | がん / 炎症 / RB / IL-6 / 代謝 / サイトカイン / ケモカイン / 乳がん / 微小環境 |
Outline of Final Research Achievements |
Retinoblastoma (RB) protein inactivation during tumor progression is often associated with a gain of immature phenotypes and chemo-resistance. Determination of an Rb inactivation signature in the context of gaining undifferentiated phenotype revealed that interleukin (IL)-6 is critically implicated in it. Breast cancers are often characterized by RB pathway inactivation. Low RB expression is linked to poorer prognosis and higher IL-6 expression in cases of breast cancer. IL-6 secreted from human breast cancers appeared to determine their tumor-initiating ability and chemo-resistance by promoting a positive feed forward loop between IL-6 and STAT3. The mechanism whereby RB inactivation increased IL-6 production involved fatty acid oxidation (FAO)-dependent mitochondrial metabolism. In addition, IL-6, via STAT3-mediated feedback to mitochondria, autonomously adjusts mitochondrial superoxide to levels suitable to maintain stem cell-like activity.
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Report
(3 results)
Research Products
(29 results)
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[Journal Article] Undifferentiated state induced by Rb-p53 double inactivation in mouse thyroid neuroendocrine cells and embryonic fibroblasts.2015
Author(s)
Kitajima S, Kohno S, Kondo A, Sasaki N, Nishimoto Y, Li F, Mohammed SA, Muranaka H, Nagatani N, Suzuki M, Kido Y and Takahashi C.
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Journal Title
Stem Cells
Volume: 53
Pages: 1657-1669
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Undifferentiated state induced by Rb-p53 double inactivation in mouse thyroid neuroendocrine cells and embryonic fibroblasts.2015
Author(s)
Kitajima S, Kohno S, Kondo A, Sasaki N, Nishimoto Y, Li F, Mohammed SA, Muranaka H, Nagatani N, Suzuki M, Kido Y and Takahashi C
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Journal Title
Stem Cells
Volume: epub
Pages: epub
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Association of prognosis of acute myeloid leukemia patients with leukemia stem cell gene signature based on nucleostemin promoter activity2014
Author(s)
Mohamed A.E. Ali, Naka K, Yoshida A, Fuse K, Kasada A, Hoshii T, Tadokoro Y, Ueno M, Ohta K, Kobayashi M, Takahashi C and Hirao A
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Journal Title
Biochem Biophys Res Commun
Volume: 450
Pages: 837-843
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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