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Chromatin remodeling in malignant progression of head-and-neck squamous cell carcinomas

Research Project

Project/Area Number 19K10080
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionKanagawa Dental College

Principal Investigator

Kurata Shun-ichi  神奈川歯科大学, 歯学部, 特任教授 (60140901)

Co-Investigator(Kenkyū-buntansha) 加藤 伊陽子  神奈川歯科大学, 歯学部, 特任教授 (20333297)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords頭頸部扁平上皮癌 / TP63 / 扁平上皮癌 / 悪性転化 / クロマチン / p63 / 頭頚部癌
Outline of Research at the Start

頭頸部扁平上皮癌の悪性化機構を明らかにするため、p63の実験系を基盤に、ゲノムワイドなクロマチンの構造変換と、表皮細胞分化に関係する遺伝子発現の変化を関連づける。
1.p63は頭頸部癌で分化型維持に作用する核内制御因子と考え、高分化型の癌細胞株がp63を失うことによって起こる、ヒストン修飾およびDNAメチル化の変化をゲノム配列上にマップする。
2.異なるステージの癌細胞株でのヒストン修飾とDNAメチル化の差異をゲノム上にマップする。加えて遺伝子発現プロファイルを解析して、クロマチン構造変化と対応させる。
3.悪性度の異なる癌組織からなる組織アレイ(匿名化)において上記の実験結果を検証する。

Outline of Final Research Achievements

To understand the mechanism of malignant progression of head-and-neck carcinomas, we performed genome editing targeting TP63 gene which is essential for epidermal cell differentiation. The knockout cells showed massive changes in gene expression profile characteristic to epithelial to mesenchymal transition, an event observed in cancer progression. Furthermore, DNA methylation and demethylation selectively occurred in the promoter and body of genes, indicating chromatin remodeling. These results suggest that the process of malignant progression of head-and-neck carcinomas is controlled epigenetically.

Academic Significance and Societal Importance of the Research Achievements

本研究では頭頸部扁平上皮癌の細胞株を実験系とし、高分化型の癌が浸潤癌に進行する過程で起こる核内の変化を解析した。得られた結果は、DNAメチル化・脱メチル化を中心とするクロマチン・リモデリングによって、遺伝子発現プロファイルが大きく変化し、上皮間葉転換(浸潤能獲得)が起こることを示唆した。癌の悪性転化を理解するには、個々の遺伝子の変異に加えて、ゲノムワイドなクロマチン構造の変化とそれが起こる機構を解析することが重要と思われる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (3 results)

All 2021 2019

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (1 results)

  • [Journal Article] C-terminal α Domain of p63 Binds to p300 to Coactivate β-Catenin2019

    • Author(s)
      Katoh Iyoko, Maehata Yojiro, Moriishi Kohji, Hata Ryu-Ichiro, Kurata Shun-ichi
    • Journal Title

      Neoplasia

      Volume: 21 Issue: 5 Pages: 494-503

    • DOI

      10.1016/j.neo.2019.03.010

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] C-X-C Motif Chemokine Ligand 14 is a Unique Multifunctional Regulator of Tumor Progression. International Journal of Molecular2019

    • Author(s)
      Xiao-Yan Yang,Shigeyuki Ozawa, Yasumasa Kato, Yojiro Maehata, Kazuhito Izukuri1, Takeharu Ikoma, Keisuke Kanamori, Tetsu Akasaka, Kenji Suzuki, Hiroshi Iwabuchi, Shun-Ichi Kurata, Iyoko Katoh,, Takashi Sakurai, Tohru Kiyono, Ryu-Ichiro Hata
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 8 Pages: 1872-1872

    • DOI

      10.3390/ijms20081872

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Impacts of TA-p63 specific exon knockout by genome editing: DeltaN-p63 silencing and loss of cell differentiation2021

    • Author(s)
      Iyoko KATOH, Ryu-Ichiro HATA and Shun-ichi Kurata
    • Organizer
      第80回日本癌学会+総会
    • Related Report
      2021 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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