Analysis of p62 nuclear - cytoplasm shuttling in the carcinogenesis of oral cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03846
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: University of Tsukuba
• Principal Investigator: Toru Yanagawa 筑波大学, 医学医療系, 教授 (10312852)
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: p62 / シャトリング / 口腔癌

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.

Free Research Field

口腔外科学

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。