| Project/Area Number |
15H05018
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | University of Yamanashi |
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Principal Investigator |
SAITOH Masao 山梨大学, 大学院総合研究部, 教授 (90345041)
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| Research Collaborator |
Ishii Hiroki
Sakamoto Kei
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
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| Keywords | EMT / 上皮間葉転換 / がん細胞 / ZEB1 / 浸潤 / 口腔癌 / CTC / TGF-beta |
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| Outline of Final Research Achievements |
The epithelial-mesenchymal transition (EMT) is an essential biological process during embryonic development, as well as during wound healing and tissue regeneration in adult tissues. The pathological significance of EMT in cancer remains controversial. It is clear, however, that ZEBs, representative EMT transcription factors, promote cancer progression by promoting invasion and drug resistance, but not tumorigenesis, as recently determined by numerous in vitro and in vivo studies using mouse cancer models.
ESE1, a member of the Ets transcription factor family, was repressed by activation of MEK-ERK pathway, resulting in induction of ZEBs through Ets1 upregulation. Conversely, Ets1 was repressed by inactivation of MEK-ERK pathway, resulting in reduction of ZEBs through ESE1 upregulation. These findings suggest that ESE1 and Ets1, whose expressions are reciprocally regulated by MEK-ERK pathway, define the EMT phenotype through controlling expression of ZEBs in cancer cells.
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| Academic Significance and Societal Importance of the Research Achievements |
がん細胞の分化度は、癌の予後を判断する上で非常に重要な因子のひとつである。その分化度を規定しているのがEMTとよばれる現象で、最近話題のがん幹細胞の発生にも寄与していると考えられている。しかしながらEMTを選択的に診断できるような分子マーカーは無く、もしEMTを獲得した細胞を効率良く診断できれば、画期的な診断法のみならず￥革新的な治療法に展開できる。本研究では、EMT時におこる非常にユニークな選択的スプライシング変化に着目し、研究をおこなった。しかしながら、現時点まで、有効な分子マーカーは同定されておらず、現在も継続して、研究を進めている。
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