Development of targeting cancer therapy against TMEPAI using macrocyclic peptide
| Project/Area Number |
18K06682
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47040:Pharmacology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | がん促進タンパク質 / TMEPAI / 結合環状ペプチド / 特殊環状ペプチド / 抗腫瘍薬 / TMEPAI/PMEPA1 / 癌関連タンパク質 / LDLRAD4 / 抗腫瘍 / 新規抗がん剤 |
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| Outline of Final Research Achievements |
TMEPAI is a transmembrane protein which is highly expressed in many types of cancer. The knock-out of TMEPAI in breast cancer cells shows less tumorigenic and lung metastatic abilities, thus TMEPAI potentiates oncogenic properties in cancer cells. Additionally we found that the tumors obtained from TMEPAI knock-out cells reduced the expression of VEGF and IL-8 that are well-known proangiogenic factors.
Moreover, we revealed that TMEPAI is involved in resistance for anti-tumor drugs in triple negative breast cancer cells and the PY motifs in intracellular region of TMEPAI are responsible for the regulation of Wnt signaling pathway. We screened TMEPAI binding macrocyclic peptide and obtained several high affinity binders. Hence we try to apply these macrocyclic peptides for clinical usage.
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| Academic Significance and Societal Importance of the Research Achievements |
乳がんは女性に最も多いがんであり、特にトリプルネガティブ乳がんは分子標的療法の選択肢も少なく、悪性度の高いがんである。TMEPAIはトリプルネガティブ乳がん細胞において、がんを促進することを明らかにしており、TMEPAIの発現を抑えることや、TMEPAIの機能を抑制することで抗腫瘍効果が示唆される。また、TMEPAIの分子メカニズムを明らかにすることで、TMEPAIを標的とした治療や診断法の開発に繋がると考えられる。今回、TMEPAIに結合する特殊環状ペプチドが得られたことで、これらの最適化を行うことで、臨床応用が期待できる。
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Report
(4 results)
Research Products
(11 results)
