Investigation of the effect of the tissue microenvironment on tumor cells through TRPV4 channel
| Project/Area Number |
16K11738
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | National Hospital Organization, Kyushu Medical Center (Clinical Institute) |
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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)
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| 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)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| Keywords | 癌 / TRPチャネル / Hippoシグナル / 口腔がん / 扁平上皮がん / がん |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(9 results)
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[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.
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Journal Title
Related Report
Peer Reviewed
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[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.
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Journal Title
Oncol. Lett.
Volume: 11
Pages: 3369-3376
Related Report
Peer Reviewed
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