Analysis of p62 nuclear - cytoplasm shuttling in the carcinogenesis of oral cancer
| Project/Area Number |
19H03846
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 57060:Surgical dentistry-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Toru Yanagawa 筑波大学, 医学医療系, 教授 (10312852)
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| Co-Investigator(Kenkyū-buntansha) |
田渕 克彦 信州大学, 学術研究院医学系, 教授 (20546767)
蕨 栄治 筑波大学, 医学医療系, 講師 (70396612)
山縣 憲司 筑波大学, 医学医療系, 准教授 (00420084)
内田 文彦 筑波大学, 医学医療系, 講師 (70736008)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | p62 / シャトリング / 口腔癌 / 口腔がん |
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| Outline of Research at the Start |
本研究では、p62の口腔癌の発癌における役割を調べるために、とくにp62の核-細胞質シャトリングに着目し、ゲノム編集を用いてp62の核排出シグナル（NES: Nuclear export signal）に遺伝子操作を加えることによってp62の核排出をON/OFFにできるノックインマウスを製作し、生体内でp62の核移行に障害が起きた際のマウスの発癌の変化の検討と、ヒトの臨床検体の前癌病変におけるp62の局在に異常がないかを免疫組織学的に検討して、p62の核-細胞質シャトリングが口腔癌の発癌において果たしている役割を探る。
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| Outline of Final Research Achievements |
In this study, we analyzed the role of p62 in oral carcinogenesis, focusing on the nuclear-cytoplasmic shuttling of p62 and how the subcellular localization of p62 affects carcinogenesis. When the nuclear efflux function was stopped by leptomycin B treatment, accumulation of p62 in the nucleus was observed. Phenotypic analysis of mice with mutations in the nuclear efflux and nuclear localization signals revealed abnormalities in kidney podcyte cells. In addition, using samples of clinical specimens of leukoplakia, we examined the association between nuclear localization of p62 and clinical indexes and pathological morphology, and proved that it was significantly associated with epithelial dysplasia. From the above, it was inferred that abnormal localization of p62 could be associated with carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではp62という選択的オートファジー（自食作用）を行う物質が口腔癌の発癌にどのように働いているかを、p62の核-細胞質の移動に注目して解析をおこなったところ、核排出シグナルと核局在シグナルに変異を加えたマウスを制作して表現型を解析したところ、核排出シグナルに異常があると細胞に異常を認め、また、前癌病変である白板症との関連を人の病理検体を用いて調べたところ、上皮異形と有意に関連することが証明されたため、p62の細胞内の局在が発癌に重要な役割をしていることが考えられた。
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Report
(4 results)
Research Products
(8 results)
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[Journal Article] Gender difference in development of steatohepatitis in <i>p62/Sqstm1 and Nrf2</i> double-knockout mice2020
Author(s)
Watahiki T, Okada K, Warabi E, Nagaoka T, Suzuki H, Ishige K, Yanagawa T, Takahashi S, Mizokami Y, Tokushige K, Ariizumi SI, Yamamoto M, Shoda J
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Journal Title
Experimental Animals
Volume: 69
Issue: 4
Pages: 395-406
DOI
NAID
ISSN
0007-5124, 1341-1357, 1881-7122
Related Report
Peer Reviewed / Open Access
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[Journal Article] Association between p62 expression and clinicopathological characteristics in oral leukoplakia.2019
Author(s)
T. Yoshida, T. Terabe, H. Nagai, F. Uchida, S. Hasegawa, T. Nagao, S. Miyabe, N. Ishibashi‐Kanno, K. Yamagata, E. Warabi, M. Gosho, T. Yanagawa, H. Bukawa
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Journal Title
Clinical and Experimental Dental Research
Volume: 5
Issue: 4
Pages: 389-397
DOI
NAID
Related Report
Peer Reviewed / Open Access
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