2023 Fiscal Year Final Research Report
Primary cilia as a novel therapeutic target in invasive bladder cancer
| Project/Area Number |
20K07601
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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 50010:Tumor biology-related
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| Research Institution | Kansai Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
田中 進 長崎県立大学, 看護栄養学部, 教授 (30399472)
大江 知里 大阪公立大学, 大学院医学研究科, 准教授 (40469242)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | 一次繊毛 / IFT88 |
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| Outline of Final Research Achievements |
In this study, we investigated the role of primary cilia protein, particularly IFT88, as a novel therapeutic target in invasive bladder cancer. Immunohistochemistry and RNA scope analyses using human samples revealed high expression of IFT88 in normal urothelium, whereas its expression was significantly reduced or lost in dysplasia and urothelial carcinoma. Attempts to establish IFT88 knockout bladder cancer cell lines using CRISPR-Cas9 were challenging. Consequently, we created conditional knockout mice with Krt5-positive cell-specific deletion of IFT88. These mice, along with wild-type counterparts, were subjected to N-butyl-N-nitrosamine administration to compare the growth and invasion rates of bladder cancer. We found that compared to wild-type mice, the loss of IFT88 accelerated the growth and invasion of bladder cancer.
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| Free Research Field |
尿路上皮癌
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| Academic Significance and Societal Importance of the Research Achievements |
これまで国内外の研究により乳癌、甲状腺癌、基底細胞癌、膵癌で一次繊毛と各癌進展の関連性、またそれにかかわるメカニズムの解明が試みられている(Gradilone et al. Curr DrugTargets 2018)。しかしながら、膀胱癌の進展と一次繊毛との関連を示した報告はない。本研究成果は、一次繊毛を構成するIFT88欠損が非筋層浸潤性膀胱癌が筋層浸潤性膀胱癌治療へ進行する際のトリガーになり得ることを示唆し、今後の新規治療ターゲット探索において重要な研究結果となった。
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