Elucidation of renal tumorigenesis driven by FLCN deficiency
| Project/Area Number |
16K11020
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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 |
Urology
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
矢尾 正祐 横浜市立大学, 医学研究科, 教授 (00260787)
近藤 慶一 横浜市立大学, 附属病院, 准教授 (80363836)
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| Research Collaborator |
Hirano Hisashi
Linehan W. Marston
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 腎癌抑制遺伝子 / FLCN / 癌と代謝 / 膜輸送 / 遺伝性腎癌 / BHD症候群 / FLCN/FNIP1/FNIP2複合体 / 細胞内輸送 / エピゲノム / 家族性腫瘍症候群 / 代謝と癌 / 腎癌 |
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| Outline of Final Research Achievements |
We are studying renal tumorigenesis under the deficiency of FLCN, a renal tumor suppressor and a causative gene for Birt-Hogg-Dube (BHD) hereditary kidney cancer syndrome. In this effort, we have reported several key findings (Hum Mol Genet, 26: 354, 2017) (Hum Mol Genet, 27: 2712, 2018) as well as have completed high-throughput analysis of phosphorylated protein profiles in FLCN-deficient kidney cancer cell lines and in Flcn-deficient murine kidneys, and identified several pathways critical for renal tumorigenesis driven by FLCN-deficiency. Because protein kinases may trigger cell proliferation under tumor suppressor deficiency and could be targets for molecular targeting agents, we are going to publish these data to provide mechanistic insights into renal tumorigenesis as well as foundations for the development of novel therapeutics for kidney cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
希少性遺伝性腎癌症候群の研究は、その他の一般的な非遺伝性の腎癌に対する治療薬開発に役立ちます。私達は本研究課題において、FLCNという希少性遺伝性腎癌症候群の原因遺伝子が変異を起こした時にリン酸化される蛋白質を、プロテオーム解析技術を用いて網羅的に調べ、いくつかの重要なリン酸化蛋白質を同定いたしました。蛋白質のリン酸化は、細胞増殖などに重要な役割を担っていることがあり、一方で蛋白質をリン酸化するキナーゼと呼ばれる酵素はその阻害剤が既に存在することが多いため、本研究で得られたデータは新規腎癌治療薬開発に役立つと考えられます。今後、私達はこの成果を論文化し報告する予定です。
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Report
(4 results)
Research Products
(30 results)
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[Journal Article] FDG PET/CT after first molecular targeted therapy predicts survival of patients with renal cell carcinoma.2018
Author(s)
Nakaigawa N, Kondo K, Kaneta T, Tateishi U, Minamimoto R, Namura K, Ueno D, Kobayashi K, Kishida T, Ikeda I, Hasumi H, Makiyama K, Hayashi N, Osaka K, Muraoka K, Izumi K, Kawahara T, Teranishi JI, Miyoshi Y, Yumura Y, Uemura H, Inoue T, Yao M.
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Journal Title
Cancer Chemother Pharmacol.
Volume: 81
Issue: 4
Pages: 739-744
DOI
Related Report
Peer Reviewed
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[Journal Article] Folliculin Regulates Osteoclastogenesis Through Metabolic Regulation2018
Author(s)
3.Baba M, Endoh M, Ma W, Toyama H, Hirayama A, Nishikawa K, Takubo K, Hano H, Hasumi H, Umemoto T, Hashimoto M, Irie N, Esumi C, Kataoka M, Nakagata N, Soga T, Yao M, Kamba T, Minami T, Ishii M, and Suda T.
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Journal Title
Journal of Bone and Mineral Research
Volume: 33
Issue: 10
Pages: 1785-1798
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Establishment and characterization of BHD-F59RSVT, an immortalized cell line derived from a renal cell carcinoma in a patient with Birt-Hogg-Dube syndrome2017
Author(s)
Furuya M, Hasumi H, Baba M, Tanaka R, Iribe Y, Onishi T, Nagashima Y, Nakatani Y, Isono Y, Yao M.
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Journal Title
Laboratory Investigation
Volume: 97
Issue: 3
Pages: 343-351
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] H255Y and K508R missense mutations in tumour suppressor folliculin (FLCN) promote kidney cell proliferation.2017
Author(s)
Hasumi H, Hasumi Y, Baba M, Nishi H, Furuya M, Vocke CD, Lang M, Irie N, Esumi C, Merino MJ, Kawahara T, Isono Y, Makiyama K, Warner AC, Haines DC, Wei MH, Zbar B, Hagenau H, Feigenbaum L, Kondo K, Nakaigawa N, Yao M, Metwalli AR, Marston Linehan W, Schmidt LS
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Journal Title
Human Molecular Genetics
Volume: 26
Pages: 354-366
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Nutrient-induced FNIP degradation by SCFβ-TRCP regulates FLCN couplex localization and promotes renal cancer progression2016
Author(s)
Nagashima, K., Fukushima, H., Shimizu, K., Hidaka, M., Hasumi, H., Ikebe, T., Fukumoto, S., Okabe, K., Inuzuka, H.
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Journal Title
Oncotarget
Volume: 8
Issue: 6
Pages: 9947-9960
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genetic, epidemiologic and clinicopathologic studies of Japanese Asian patients with Birt-Hogg-Dube syndrome.2016
Author(s)
Furuya M, Yao M, Tanaka R, Nagashima Y, Kuroda N, Hasumi H, Baba M, Matsushima J, Nomura F, Nakatani Y
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Journal Title
Clinical Genetics
Volume: 90
Issue: 5
Pages: 403-412
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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