| Project/Area Number |
17K08766
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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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| Research Field |
Experimental pathology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 細胞間接着 / がん / 細胞競合 / 腫瘍内不均一性 / 癌 / 細胞・組織 / 発現制御 |
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| Outline of Final Research Achievements |
Various molecules, including cell adhesion molecule claudins (CLDN), are aberrantly expressed in cancer cells. We have discovered a novel signaling pathway from CLDN to novel serine phosphorylation of nuclear receptors that regulates tomour malignacy in breast and endometrial cancers. On the other hand, we found that one CLDN molecule regulates the expression of another CLDN molecule in cultured cancer cell lines and human cancer tissues. In particular, CLDN4 and CLDN6 were exclusively distributed, and CLDN4-positive or CLDN6-positive cells have different features not only in intercellular adhesion, but also in cell polarity or proliferation. These results indicate that the CLDN expression pattern may be a useful cancer biomarker for personalized treatment.
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| Academic Significance and Societal Importance of the Research Achievements |
CLDN分子の相互発現制御を解明することにより、異種CLDNどうしのタンパクレベルでの発現制御機構といった新たな生命現象を提唱できる可能性がある。また本機構によってがん組織に発生するCldn分子の多彩な発現様式が腫瘍内不均一性を示し、がんの分化度や悪性度に関連することが明らかになれば、診断並びに予後不良の新たな指標となることが見込まれる。さらｎ異なるCLDN分子を発現誘導することにより、がんの悪性化に繋がるCLDN発現を抑制するという、新規分子標的療法の開発に繋がることが期待される。
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