| Project/Area Number |
17K18301
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Surgical dentistry
Pathobiological dentistry/Dental radiology
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| Research Institution | Fukuoka Dental College |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 口腔扁平上皮癌 / 癌微小環境 / 高浸透圧 / 浸透圧 |
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| Outline of Final Research Achievements |
In the tumor microenvironment, tumor usually incites inflammation and the inflammation-derived cytokines make a considerable impact on cancer development. In this condition, hyper-osmolarity is also induced but the role of the osmotic stress for the cancer development has not been fully understood. In this study, we clarified one of the essential mechanisms of NFAT5, a key transcription factor in hyper-osmolarity, on the OSCC cells in the hyper-osmotic condition by in vitro and in vivo studies. We finally concluded that in OSCC cells in the hyper-osmotic condition, NFAT5 induced EGFR glycosylation through the activation of DPAGT1, an essential enzyme for the N-linked protein glycosylation, and the consecutive EGFR subcellular translocation from the endoplasmic reticulum to the plasma membrane was occurred, which finally enhanced the progression of OSCC cells.
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| Academic Significance and Societal Importance of the Research Achievements |
転写因子であるNFAT5（nuclear factor of activated T-cells 5）が核内移行・活性化し、細胞にかかる高浸透圧ストレスを解消する遺伝子の発現に関与しているとされています。最近我々はNFAT5が口腔癌細胞の進展に関与していることを報告しました。現在、癌微小環境を対象とした研究においては、「低酸素」、「低栄養」に着目した研究が広く行われていますが、未だ報告の少ない「浸透圧」の癌細胞への関与を解き明かすことで、癌治療に対する新たなアプローチとなる可能性が考えられます。
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