Fluctuation of ectodomain shedding and the emersion of cancer cell heterogeneity
Project/Area Number |
16K15221
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
General medical chemistry
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Research Institution | Ehime University |
Principal Investigator |
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Co-Investigator(Renkei-kenkyūsha) |
NAKAYAMA HIROINAO 愛媛大学, プロテオサイエンスセンター, 助教 (40512132)
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Research Collaborator |
FUKUDA SHINJI 愛媛大学, プロテオサイエンスセンター, 講師 (70398238)
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Project Period (FY) |
2016-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | がん細胞の不均一性 / 乳がん細胞 / ゆらぎ / EGFファミリー / エクトドメイン・シェディング / amphiregulin / CUL3 / RhoA / 膜型細胞増殖因子 / Amphiregulin / エクトドメイン・シェディング” / アクチンダイナミクス / cullin3 / ユビキチンE3リガーゼシ / proHB-EGF / proamphiregulin / シェディング / ADAM |
Outline of Final Research Achievements |
Cancer is derived a single cell and becomes to show heterogeneous population during the growth of its mass in general, which seems to lead to drug resistance. The epidermal growth factor (EGF) family are transmembrane growth factors and their ectodomain shedding is a crucial event to determine their soluble growth factor levels. We speculate that the fluctuation of the ectodomain shedding of the EGF family would be related to the emersion of heterogeneous population of cancer. In this study, we at first established three clones, stem, basal and luminal types, form human breast cancer cell line, MCF-7 cells, and then performed quantitative analysis of the ectodomain shedding of EGF family ligands in these clones. We revealed that the ectodomain shedding of proAREG uniquely showed the correlation between the shedding level and clone types, and was regulated through actin dynamics by CUL3 -RING based E3 ubiquitin ligase-dependent Rho activation.
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Report
(3 results)
Research Products
(10 results)
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[Journal Article] Stimulated release and functional activity of surface expressed metalloproteinase ADAM17 in exosomes.2016
Author(s)
Groth E, Pruessmeyer J, Babendreyer A, Schumacher J, Pasqualon T, Dreymueller D, Higashiyama S, Lorenzen I, Grotzinger J, Cataldo D, Ludwig A.
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Journal Title
Biochim Biophys Acta.
Volume: 1863
Issue: 11
Pages: 2795-2808
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Ectodomain Shedding of Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1) is induced by VEGF-A.2016
Author(s)
Nishida-Fukuda H, Araki R, Shudou M, Okazaki H, Tomono Y, Nakayama H, Fukuda S, Sakaue T, Shirakata Y, Sayama K, Hashimoto K, Detmar M, Higashiyama S, Hirakawa S.
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Journal Title
J Biol Chem.
Volume: 291
Issue: 20
Pages: 10490-10490
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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