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Elucidation of mechanotransduction mechanisms in oral squamous cell carcinoma cells with high CD44 expression

Research Project

Project/Area Number 20K10138
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

Shigeishi Hideo  広島大学, 医系科学研究科(歯), 講師 (90397943)

Co-Investigator(Kenkyū-buntansha) 小野 重弘  広島大学, 医系科学研究科(歯), 助教 (70379882)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords癌幹細胞 / CD44 / アポトーシス抵抗性 / メカニカルストレス / 口腔癌 / シリコンゲル / 口腔扁平上皮癌 / amoeboid-like CD44high細胞 / AMT
Outline of Research at the Start

幹細胞は自己複製能と分化能をもつ細胞であるが、癌組織においても癌特異的な幹細胞が存在し、腫瘍の再発や転移に深く関与すると考えられている。本研究においては、これまでの成果をさらに発展させ、微小環境やメカニカルストレスにより制御される、新たなヒト口腔癌幹細胞の分化制御機構を明らかにする。さらに癌幹細胞において制御される個々の遺伝子産物の発現と機能を検討し、口腔扁平上皮癌における高度悪性化機構の解明を目指す。

Outline of Final Research Achievements

Cofilin-1, an intracellular actin-modulating protein, was involved in the invasive capacity of CD44high OSCC cells. TGF-β1 induced amoeboid-to-mesenchymal transition by Cofilin-1 phosphorylation and downregulation of miR-422a via ERK activation. Our findings suggest that miR-422a and Cofilin-1 play major roles in the maintenance of amoeboid-like CD44high cells. Furthermore, miR-224-5p plays a vital role in the resistance to docetaxel-induced apoptosis by attenuating PANX1-induced ATP discharge.

Academic Significance and Societal Importance of the Research Achievements

amoeboid-like CD44高発現口腔扁平上皮癌細胞は、高い浸潤能を持つことから、腫瘍の再発や転移に関与している可能性が示唆された。さらに、amoeboid-like CD44高発現口腔扁平上皮癌細胞は、口腔扁平上皮癌における抗がん剤抵抗性に関与していると予測されるため、amoeboid-like CD44高発現口腔扁平上皮癌細胞におけるアポトーシス回避機構を解明することが重要であると考えられた。

Report

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

    (3 results)

All 2022 2021

All Journal Article (3 results) (of which Peer Reviewed: 2 results)

  • [Journal Article] Melatonin enhances cisplatin-induced cell death through inhibition of DERL1 in mesenchymal-like CD44high OSCC cells.2022

    • Author(s)
      Shigeishi H, Yokoyama S, Murodumi H, Sakuma M, Fukada S, Okuda S, Yamakado N, Ono S, Takechi M, Ohta K.
    • Journal Title

      Journal of Oral Pathology & Medicine

      Volume: 51 Issue: 3 Pages: 281-289

    • DOI

      10.1111/jop.13242

    • Related Report
      2022 Annual Research Report
  • [Journal Article] TGF-β1 induces amoeboid-to-mesenchymal transition of CD44high oral squamous cell carcinoma cells via miR-422a downregulation through ERK activation and Cofilin-1 phosphorylation.2021

    • Author(s)
      Yokoyama S, Shigeishi H, Murodumi H, Sakuma M, Kato H, Higashikawa K, Ohta K, Sugiyama M, Takechi M.
    • Journal Title

      Oral Pathol Med

      Volume: 50 Issue: 2 Pages: 155-164

    • DOI

      10.1111/jop.13113

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of miR-224-5p-enhanced downregulation of PANX1 on docetaxel-induced apoptosis in amoeboid-like CD44high oral cancer cells.2021

    • Author(s)
      Yokoyama S, Shigeishi H, Murodumi H, Sakuma M, Ono S, Tobiume K, Sugiyama M, Ohta K, Takechi M.
    • Journal Title

      European Journal of Oral Sciences

      Volume: 129 Issue: 5

    • DOI

      10.1111/eos.12812

    • Related Report
      2021 Research-status Report
    • Peer Reviewed

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

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