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Involvement of EMT and cancer stem cells in the mechanism of Snail-induced acquisition of metastatic potential of oral cancer

Research Project

Project/Area Number 20K10139
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionHiroshima University

Principal Investigator

Ono Shigehiro  広島大学, 医系科学研究科(歯), 助教 (70379882)

Co-Investigator(Kenkyū-buntansha) 武知 正晃  独立行政法人国立病院機構(呉医療センター臨床研究部), その他部局等, 医師 (00304535)
飛梅 圭  広島大学, 医系科学研究科(歯), 准教授 (40350037)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords口腔癌 / 転移 / EMT / 口腔扁平上皮癌 / 癌幹細胞
Outline of Research at the Start

口腔癌の発生・進展について解析を続け,特に局所浸潤におけるEMTの関与の研究を行ってきた.EMT誘導因子であるSnail に着目し,浸潤の多様性にいかに関与しているかを探求してきた.そこでさらに,転移にも関与しているのではないかと考えた.一方で,高度浸潤型癌細胞の一部は癌幹細胞形質を獲得していることを確認している.これらのことから,Snail誘導型EMT型癌細胞が癌幹細胞様形質を獲得し,転移をするのではないかと仮説を立て,その実験モデルを作成することを目的とした.本課題を解明した場合には,本遺伝子を標的とした分子標的治療の有力な候補遺伝子となりうると考え,新しい癌治療の開発が期待できる.

Outline of Final Research Achievements

We have been focusing on EMT as one of the mechanisms of cancer invasion and metastasis. The purpose of this study was to elucidate the mechanism of EMT in the acquisition of high invasive potential of oral cancer, which is thought to be induced by Snail. The results suggest that Snail may be involved in the invasive and metastatic potential of oral squamous cell carcinoma via EMT and that Snail possesses stem cell-like traits. On the other hand, Snail may be involved in the acquisition of cancer stem cell traits and consequently induces EMT, resulting in the acquisition of invasive metastatic potential. These results suggest that Snail may be a potential target for the regulation of cancer invasion and metastasis.

Academic Significance and Societal Importance of the Research Achievements

口腔癌の浸潤・転移機構に関して詳細は現在まで十分に解明されていない.特に,口腔癌の転移は患者の予後に大きく影響を与える.これまでにわれわれは一つの候補としてEMTを介した高度浸潤能獲得機構について研究を継続している.本研究の結果により,EMTを介した口腔癌の浸潤・転移獲得機構と幹細胞形質の獲得にSnailが関与している可能性が示唆された.本遺伝子が比較的予後の悪いとされる口腔癌の浸潤と転移を制御しうる口腔癌治療の標的になりうると考えられた.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (3 results)

All 2023 2022

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] Chemical inhibition of LSD1 leads to epithelial to mesenchymal transition in vitro of an oral squamous cell carcinoma OM-1 cell line via release from LSD1-dependent suppression of ZEB1.2023

    • Author(s)
      Yamakado N, Okuda S, Tobiume K, Uetsuki R, Ono S, Mizuta K, Nakagawa T, Aikawa T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: in press Pages: 23-29

    • DOI

      10.1016/j.bbrc.2023.01.062

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dexamethasone resets stable association of nuclear Snail with LSD1 concomitant with transition from EMT to partial EMT2022

    • Author(s)
      Satoshi Okuda, Nao Yamakado, Koichiro Higashikawa, RyoUetsuki, Fumi Ishida, Andra Rizqiawan, Shigehiro Ono, Kuniko Mizuta, Nobuyuki Kamata, Kei Tobiume
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 30 Pages: 101277-101277

    • DOI

      10.1016/j.bbrep.2022.101277

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 口腔癌細胞におけるデキサメタゾンによるEMTからpartial EMTへの移行2022

    • Author(s)
      山門奈央, 飛梅 圭, 奥田哲史, 植月 亮, 中川貴之, 水田邦子, 小野重弘, 相川友直
    • Organizer
      第67回(公社)日本口腔外科学会総会・学術大会
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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