| 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 |
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| Research Field |
Tumor biology
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| Research Institution | Kanazawa University |
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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)
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| 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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