Elucidation of invasion and metastasis mechanism through epithelial mesenchymal transition - mesenchymal epithelial transition in the oral squamous cell carcinoma cell
| Project/Area Number |
17K11851
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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 | Iwate Medical University |
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Principal Investigator |
Masaharu Kamo 岩手医科大学, 歯学部, 准教授 (40214564)
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| Co-Investigator(Kenkyū-buntansha) |
石崎 明 岩手医科大学, 歯学部, 教授 (20356439)
小松 祐子 岩手医科大学, 歯学部, 助教 (90781625)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 上皮間葉転換 / 間葉上皮転換 / 口腔扁平上皮癌細胞 / TGF-β1 / BMP-2 / Hippo経路 / Sox9 / Slug / 上皮間陽転換 / 細胞内シグナル伝達 / TGF-β / ケモカイン / がんの浸潤・転移 / 口腔扁平上皮癌 / 癌関連線維芽細胞 / がんの転移 / 癌 / シグナル伝達 |
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| Outline of Final Research Achievements |
In human oral squamous cell carcinoma cell HSC-4 cells, (1) TGF-β1 induced the epithelial-mesenchymal transition (EMT), whereas it is suggested that BMP-2 induced the mesenchymal-epithelial transition (MET). (2) In TGF-β1-induced EMT, the transcription factors Slug suppressed the expression of E-cadherin, whereas Sox9 increased expression of N-cadherin. (3) In the low cell density, disruption of the adhesion between the cells by E-cadherins induced activation of YAP/TAZ, and increased expression of N-cadherin through the promotion of nuclear localization of Slug. (4) The expression of tumor suppressor CXCL14 induced by EMT was suppressed by CCL20 derived from the macrophage.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、まだ理解が進んでいない、ヒト口腔扁平上皮癌細胞の浸潤・転移を制御する分子とそのシグナルに関する研究行なっている。HSC-4細胞がTGF-βとBMPの両者に応答する細胞株であり、EMT/METによる浸潤・転移のモデルとして非常に有用であることが示された。EMTに関しては、癌の悪性化に関わる転写因子の同定と、これがHippo経路により制御されていることが示された。また、マクロファージとの相互作用に癌細胞の悪性化に関与するケモカインが関与していることが見出された。これらの理解が進めば、口腔癌治療のための新たな標的分子になる可能性があると考えられる。
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] Toll-like receptor 4-mediated signaling activated by lipopolysaccharide suppresses transforming growth factor-beta-induced nerve growth factor expression in periodontal ligament-derived fibroblasts2018
Author(s)
Ohta M.*, Nemoto A.*, Chosa N., Kyakumoto S., Yokota S., Kamo M., Shibata S., Joh S., Satoh K., Ishisaki A.
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Journal Title
Dental Journal of Iwate Medical University
Volume: 43
Issue: 1
Pages: 61-73
DOI
NAID
ISSN
0385-1311, 2424-1822
Year and Date
2018-05-25
Related Report
Peer Reviewed / Open Access
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[Journal Article] IL-1β and TNF-α suppress TGF-β-promoted NGF expression in periodontal ligament-derived fibroblasts through inactivation of TGF-β-induced Smad2/3-, and p38 MAPK-mediated signals2018
Author(s)
Ohta M., Chosa N., Kyakumoto S., Yokota S., Okubo N., Nemoto A., Kamo M., Joh S., Satoh K., Ishisaki A.
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Journal Title
International Journal of Molecular Medicine
Volume: 43
Pages: 1484-1494
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Transforming growth factor-β1 suppresses bone morphogenetic protein-2-induced mesenchymal-epithelial transition in HSC-4 human oral squamous cell carcinoma cells via Smad1/5/9 pathway suppression.2017
Author(s)
Chiba, T., Ishisaki, A., Kyakumoto, S., Shibata, T., Yamada, H., and Kamo, M.
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Journal Title
Oncol. Rep.
Volume: 37
Issue: 2
Pages: 713-720
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] ROCK/actin/MRTF signaling promotes the fibrogenic phenotype of fibroblast-like synoviocytes derived from the temporomandibular joint.2017
Author(s)
Yokota, S., Chosa, N., Kyakumoto, S., Kimura, H., Ibi, M., Kamo, M., Satoh, K., and Ishisaki, A.
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Journal Title
Int. J. Mol. Med.
Volume: 39
Issue: 4
Pages: 799-808
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and -dependent manners under hypoxic culture2017
Author(s)
Takizawa N, Okubo N, Kamo M, Chosa N, Mikami T, Suzuki K, Yokota S, Ibi M, Ohtsuka M, Taira M, Sasaki D, Yaegashi T, Ishisaki A, Kyakumoto S
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Journal Title
Experimental Cell Res.
Volume: 358
Issue: 2
Pages: 411-420
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] ヒト口腔扁平上皮癌細胞の上皮間葉転換におけるHippo経路の関与2018
Author(s)
平野大輔, 齋藤大嗣,小松祐子,千葉高大, 樋野雅文, 横田 聖司, 客本齊子,帖佐直幸,山田浩之, 石崎 明, 加茂政晴
Organizer
日本生化学会東北支部第84回例会・シンポジウム
Related Report
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