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DOI | 10.1038/s41467-019-11771-z |
Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity | |
Hernandez-Fernaud, Juan R.1; Ruengeler, Elena1; Casazza, Andrea2; Neilson, Lisa J.1; Pulleine, Ellie3; Santi, Alice1; Ismail, Shehab1; Lilla, Sergio1; Dhayade, Sandeep1; MacPherson, Iain R.4; McNeish, Iain4; Ennis, Darren4; Ali, Hala5,6; Kugeratski, Fernanda G.1; Al Khamici, Heba5,6; van den Biggelaar, Maartje7; van den Berghe, Peter V. E.1; Cloix, Catherine1; McDonald, Laura1; Millan, David8; Hoyle, Aoisha8; Kuchnio, Anna9; Carmeliet, Peter9; Valenzuela, Stella M.5,6; Blyth, Karen1; Yin, Huabing3; Mazzone, Massimiliano2; Norman, Jim C.1; Zanivan, Sara1 | |
2019-09-03 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Scotland; Belgium; Australia; Netherlands |
英文摘要 | The secretome of cancer and stromal cells generates a microenvironment that contributes to tumour cell invasion and angiogenesis. Here we compare the secretome of human mammary normal and cancer-associated fibroblasts (CAFs). We discover that the chloride intracellular channel protein 3 (CLIC3) is an abundant component of the CAF secretome. Secreted CLIC3 promotes invasive behaviour of endothelial cells to drive angiogenesis and increases invasiveness of cancer cells both in vivo and in 3D cell culture models, and this requires active transglutaminase-2 (TGM2). CLIC3 acts as a glutathione-dependent oxidoreductase that reduces TGM2 and regulates TGM2 binding to its cofactors. Finally, CLIC3 is also secreted by cancer cells, is abundant in the stromal and tumour compartments of aggressive ovarian cancers and its levels correlate with poor clinical outcome. This work reveals a previously undescribed invasive mechanism whereby the secretion of a glutathione-dependent oxidoreductase drives angiogenesis and cancer progression by promoting TGM2-dependent invasion. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000394215600001 |
WOS关键词 | IN-VITRO MODEL ; GENE-EXPRESSION ; STROMAL CELLS ; TUMOR MICROENVIRONMENT ; TRANSGLUTAMINASE 2 ; LYSYL OXIDASE ; HUMAN BREAST ; MAJOR ROLE ; FIBROBLASTS ; INTEGRIN |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204521 |
专题 | 资源环境科学 |
作者单位 | 1.Canc Res UK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland; 2.VIB, Vesalius Res Ctr, Lab Mol Oncol & Angiogenesis, B-3000 Leuven, Belgium; 3.Univ Glasgow, Sch Engn, Div Biomed Engn, Glasgow G12 8LT, Lanark, Scotland; 4.Univ Glasgow, Wolfson Wohl Canc Res Ctr, Inst Canc Sci, Glasgow G61 1QH, Lanark, Scotland; 5.Univ Technol Sydney, Sch Life Sci, Sydney, NSW 2007, Australia; 6.Univ Technol Sydney, Ctr Hlth Technol, Sydney, NSW 2007, Australia; 7.Dept Plasma Prot Sanquin Res, NL-1066 CX Amsterdam, Netherlands; 8.Queen Elizabeth Univ Hosp, Dept Pathol, Glasgow G51 4TF, Lanark, Scotland; 9.VIB Ctr Canc Biol, Vesalius Res Ctr, Lab Angiogenesis & Vasc Metab, B-3000 Leuven, Belgium |
推荐引用方式 GB/T 7714 | Hernandez-Fernaud, Juan R.,Ruengeler, Elena,Casazza, Andrea,et al. Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity[J]. NATURE COMMUNICATIONS,2019,8. |
APA | Hernandez-Fernaud, Juan R..,Ruengeler, Elena.,Casazza, Andrea.,Neilson, Lisa J..,Pulleine, Ellie.,...&Zanivan, Sara.(2019).Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity.NATURE COMMUNICATIONS,8. |
MLA | Hernandez-Fernaud, Juan R.,et al."Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity".NATURE COMMUNICATIONS 8(2019). |
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