Elucidation of the molecular mechanisms by which DPP-4 plays a role in the development and metastasis of malignant tumors
| Project/Area Number |
18K16214
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
TAKAGAKI Yuta 金沢医科大学, 医学部, 助教 (50759123)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 糖尿病 / DPP-4 / 癌 / 乳癌 / 上皮間葉系細胞分化 / CXCL12/CXCR4 / mTOR / インクレチン / EMTプログラム |
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| Outline of Final Research Achievements |
In vitro, DPP-4 inhibitor treatment induced EMT program by activating mTOR in a CXCL12/CXCR4 signaling-dependent manner, and in vivo, CXCR4 inhibitor treatment reduced tumor size and suppressed metastasis. In addition, DPP-4 knockdown breast cancer cells acquired resistance to doxorubicin through induction of the EMT program. Using surgical specimens, we found that DPP-4 expression was increased and CXCR4 expression was decreased in Stage I breast cancer tissues, while DPP-4 expression was decreased and CXCR4 expression was increased in Stage IV breast cancer tissues.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病患者は癌のリスクが上昇することが知られており、2倍以上リスクが増加する癌種もあり、糖尿病治療薬により発癌、病期進行を来す可能性に関しては十分な検討が必要である。本研究の結果は現在、その優れた血糖降下作用や低血糖リスクの少なさから、高齢者を含めた多くの患者に使用されている、DPP-4阻害薬の新たなリスクの可能性を明らかにすることで、より病態に応じた使い分けを行う指標となる。
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Report
(4 results)
Research Products
(3 results)
