• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of TRP signal activation mechanism in tumor-stromal seqence in oral tumor and its clinical application

Research Project

Project/Area Number 22K17017
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 57020:Oral pathobiological science-related
Research InstitutionKyushu University

Principal Investigator

Tajiri Yudai  九州大学, 歯学研究院, 共同研究員 (30820659)

Project Period (FY) 2022-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords腫瘍実質-間質連関 / 口腔癌 / p63 / MAPK / 扁平上皮癌 / TRP / TRPV4
Outline of Research at the Start

これまでの研究で、腫瘍実質と間質が相互作用「腫瘍実質-間質連関」しながら腫瘍形成を促進することを明らかにしており、その一つにTRPV4シグナルの異常活性化が挙げられるが、詳細な分子基盤は不明である。
本研究では、口腔扁平上皮癌における、TRPV4シグナルの活性化メカニズム(発現制御機構と活性化ドメイン)を解明し、機能抑制メカニズムを明らかにすることで、TRPV4を標的とした抗腫瘍効果について解析を行う。

Outline of Final Research Achievements

The aim of this study was to elucidate the underlying mechanism which can regulate TRPV4 signals abnormally activated by the extracellular environment in oral squamous cell carcinoma (OSCC). In our established experimental setting to activate YAP signaling, it was not confirmed that TRPV4 signal expression was regulated by YAP signaling.
On the other hand, gene expression in OSCC pathological specimens was comprehensively investigated using DNA microarray method. The results suggested that p63 expression increases during the carcinogenesis process, and MAPK is activated in the invasive carcinomalesion. Furthermore, together with the research using OSCC cell lines, it is suggested that a novel oncogene ARL4C is cooperatively regulated by p63 and MEK/ERK-MAPK in OSCCs.

Academic Significance and Societal Importance of the Research Achievements

悪性腫瘍では遺伝子異常が生じるため、細胞が自律的に増殖する。本邦では、病変組織を用いて遺伝子異常を明らかにすることで、患者一人一人に適した治療法を提供できるがんゲノム医療の普及が進められている。一方、口腔癌の90%以上を占める OSCCにおける特異的な遺伝子異常が少ないため、異常活性化した細胞内シグナルが発癌に寄与すると予想される。本研究では、OSCC病理標本(非腫瘍部、上皮性異形成/上皮内癌、浸潤癌を含む)における遺伝子発現について、網羅的に検討した。本研究結果によってOSCCの発癌過程において活性化するシグナルが明らかとなった。この学術意義は高く、治療への応用の足掛かりとなる。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (3 results)

All 2023 2022 Other

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

  • [Int'l Joint Research] University of Turku(フィンランド)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Stepwise activation of p63 and the MEK/ERK pathway induces the expression of ARL4C to promote oral squamous cell carcinoma cell proliferation.2023

    • Author(s)
      Alkhatib DZR, Thi Kim Truong T, Fujii S, Hasegawa K, Nagano R, Tajiri Y, Kiyoshima T.
    • Journal Title

      Pathol Res Pract.

      Volume: 246 Pages: 154493-154493

    • DOI

      10.1016/j.prp.2023.154493

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Semaphorin 3A-AKT axis-mediated cell proliferation in salivary gland morphogenesis and adenoid cystic carcinoma pathogenesis.2022

    • Author(s)
      Fujii S, Fujimoto T, Hasegawa K, Nagano R, Ishibashi T, Kurppa KJ, Mikami Y, Kokura M, Tajiri Y, Kibe T, Wada H, Wada N, Kishida S, Higuchi Y, Kiyoshima T.
    • Journal Title

      Pathol Res Pract.

      Volume: 236 Pages: 153991-153991

    • DOI

      10.1016/j.prp.2022.153991

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research

URL: 

Published: 2022-04-19   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi