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Investigation of the effect of the tissue microenvironment on tumor cells through TRPV4 channel

Research Project

Project/Area Number 16K11738
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Surgical dentistry
Research InstitutionNational Hospital Organization, Kyushu Medical Center (Clinical Institute)

Principal Investigator

Ozeki Satoru  独立行政法人国立病院機構九州医療センター(臨床研究センター), その他部局等, 口腔腫瘍・口腔ケアセンター 口腔腫瘍統括長 (80117077)

Co-Investigator(Kenkyū-buntansha) 清島 保  九州大学, 歯学研究院, 教授 (20264054)
藤井 慎介  九州大学, 歯学研究院, 助教 (60452786)
和田 裕子  九州大学, 歯学研究院, 助教 (70380706)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords癌 / TRPチャネル / Hippoシグナル / 口腔がん / 扁平上皮がん / がん
Outline of Final Research Achievements

In this study, it was shown that the high expression of transient receptor potential vanilloid 4 (TRPV4) in oral squamous cell carcinoma (OSCC) and its function in OSCC tumorigenesis in vitro an in vivo. Several OSCC cell lines highly expressed TRPV4 mRNA and protein. Knockdown of TRPV4 with siRNA reduced TRPV4 agonist-dependent Ca2+ influx, cellular growth, migration capability and AKT activation. Treatments with TRPV4 overexpression rescued these loss-of-function effects with TRPV4 siRNA. In contrast, TRPV4 knockdown did not affect the expression of target genes of Hippo pathway signaling. Xenograft models showed that the volumes and weights of TRPV4 shRNA expressing tumor groups were less than those of control groups. These results suggest that TRPV4 expression is required for tumor formation in vitro and in vivo.

Academic Significance and Societal Importance of the Research Achievements

近年、癌細胞周囲の微小環境の変化に応答して癌細胞の細胞内シグナル伝達が活性化され、腫瘍形成が促進する知見について報告されている。TRPV4チャネルはCa2+の流入に関与するイオンチャネルファミリーとして同定され、細胞周囲の微小環境(機械ストレスや浸透圧ストレス)を感知すると考えられている。本研究ではTRPV4が口腔扁平上皮癌細胞において高発現し、細胞外周囲の環境を認識し、増殖を制御することを明らかにした。この結果は、TRPV4の活性化を標的とする新たな癌治療の開発に繋がる可能性を示している。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016

All Journal Article (5 results) (of which Peer Reviewed: 4 results) Presentation (4 results)

  • [Journal Article] GLI-mediated Keratin 17 expression promotes tumor cell growth through the anti-apoptotic function in oral squamous cell carcinomas.2017

    • Author(s)
      Mikami Y, Fujii S, Nagata K, Wada H, Hasegawa K, Abe M, Yoshimoto RU, Kawano S, Nakamura S, Kiyoshima T.
    • Journal Title

      J Cancer Res Clin Oncol.

      Volume: doi:10.1007/s00432-017-2398-2

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Critical roles of Wnt5a-Ror2 signaling in aggressiveness of tongue squamous cell carcinoma and production of matrix metalloprotease-2 via ΔNp63β-mediated epithelial-mesenchymal transition.2017

    • Author(s)
      Sakamoto T., Kawano S., Matsubara R., Goto Y., Jinno T., Maruse Y., Kaneko N., Hashiguchi Y., Hattori T., Tanaka S., Kitamura R., Kiyoshima T., Nakamura S.
    • Journal Title

      Oral Oncol.

      Volume: 未定

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Facioscapulohumeral muscular dystrophy (FSHD) region gene 1 (FRG1) expression and possible function in mouse tooth germ development.2016

    • Author(s)
      Hasegawa K, Wada H, Nagata K, Fujiwara H, Wada N, Someya H, Mikami Y, Sakai H, Kiyoshima T.
    • Journal Title

      J Mol Histol.

      Volume: 47 Pages: 375-387

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological evaluation of preoperative chemoradiotherapy with S-1 for locally advanced oral squamous cell carcinoma.2016

    • Author(s)
      Kawano S., Zheng Y., Oobu K., Matsubara R., Goto Y., Chikui T., Yoshitake T., Kiyoshima T., Jinno T., Maruse M., Mitate E., Kitamura R., Tanaka H., Toyoshima T., Sugiura T. and Nakamura S.
    • Journal Title

      Oncol. Lett.

      Volume: 11 Pages: 3369-3376

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] 顎口腔領域への転移性腫瘍についての臨床的検討2016

    • Author(s)
      矢内雄太、大山順子、窪田泰孝、杉浦剛、清島保、白砂兼光
    • Journal Title

      日口外誌

      Volume: 62 Pages: 199-204

    • NAID

      130005157224

    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト口腔癌におけるTRPV4の発現と機能解析2018

    • Author(s)
      田尻祐大、藤井慎介、大関悟、清島保
    • Organizer
      第60回歯科基礎医学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] GLI-KRT17連関は口腔扁平上皮癌における腫瘍形成を促進する2016

    • Author(s)
      三上 友理恵、清島 保
    • Organizer
      第93回九大病理研究会
    • Place of Presentation
      福岡
    • Year and Date
      2016-12-10
    • Related Report
      2016 Research-status Report
  • [Presentation] 口腔扁平上皮癌においてGli阻害剤(GANT61)は細胞死を誘導する2016

    • Author(s)
      三上友理恵、永田健吾、和田裕子、藤井慎介、安部みさき、吉本怜子、清島保、中村誠司
    • Organizer
      第58回歯科基礎医学会学術大会総会
    • Place of Presentation
      札幌
    • Year and Date
      2016-08-24
    • Related Report
      2016 Research-status Report
  • [Presentation] A case of adenosquamous carcinoma observed in the metastatic lymph node, but not in the primary lesion.2016

    • Author(s)
      三上 友理恵、和田 裕子、永田 健吾、大部 一成、中村 誠司、清島 保
    • Organizer
      第27回日本臨床口腔病理学会総会
    • Place of Presentation
      広島
    • Year and Date
      2016-08-10
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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