Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity
Hernandez-Fernaud, JR
Ruengeler, E
Casazza, A
Neilson, LJ
Pulleine, E
Santi, A
Ismail, S
Lilla, S
Dhayade, S
MacPherson, IR
McNeish, I
Ennis, D
Ali, H
Kugeratski, FG
Al Khamici, H
Van Den Biggelaar, M
Van Den Berghe, PVE
Cloix, C
McDonald, L
Millan, D
Hoyle, A
Kuchnio, A
Carmeliet, P
Valenzuela, SM
Blyth, K
Yin, H
Mazzone, M
Norman, JC
Zanivan, S
- Publication Type:
- Journal Article
- Citation:
- Nature Communications, 2017, 8
- Issue Date:
- 2017-02-15
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Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Hernandez-Fernaud, JR | en_US |
dc.contributor.author | Ruengeler, E | en_US |
dc.contributor.author | Casazza, A | en_US |
dc.contributor.author | Neilson, LJ | en_US |
dc.contributor.author | Pulleine, E | en_US |
dc.contributor.author | Santi, A | en_US |
dc.contributor.author | Ismail, S | en_US |
dc.contributor.author | Lilla, S | en_US |
dc.contributor.author | Dhayade, S | en_US |
dc.contributor.author | MacPherson, IR | en_US |
dc.contributor.author | McNeish, I | en_US |
dc.contributor.author | Ennis, D | en_US |
dc.contributor.author | Ali, H | en_US |
dc.contributor.author | Kugeratski, FG | en_US |
dc.contributor.author | Al Khamici, H | en_US |
dc.contributor.author | Van Den Biggelaar, M | en_US |
dc.contributor.author | Van Den Berghe, PVE | en_US |
dc.contributor.author | Cloix, C | en_US |
dc.contributor.author | McDonald, L | en_US |
dc.contributor.author | Millan, D | en_US |
dc.contributor.author | Hoyle, A | en_US |
dc.contributor.author | Kuchnio, A | en_US |
dc.contributor.author | Carmeliet, P | en_US |
dc.contributor.author |
Valenzuela, SM https://orcid.org/0000-0001-5934-6047 |
en_US |
dc.contributor.author | Blyth, K | en_US |
dc.contributor.author | Yin, H | en_US |
dc.contributor.author | Mazzone, M | en_US |
dc.contributor.author | Norman, JC | en_US |
dc.contributor.author | Zanivan, S | en_US |
dc.date.available | 2016-12-06 | en_US |
dc.date.issued | 2017-02-15 | en_US |
dc.identifier.citation | Nature Communications, 2017, 8 | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/125259 | |
dc.description.abstract | © The Author(s) 2017. 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. | en_US |
dc.relation.ispartof | Nature Communications | en_US |
dc.relation.isbasedon | 10.1038/ncomms14206 | en_US |
dc.subject.mesh | Cell Line, Tumor | en_US |
dc.subject.mesh | Extracellular Matrix | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Mice, Inbred C57BL | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Mice, Nude | en_US |
dc.subject.mesh | Neoplasms | en_US |
dc.subject.mesh | Neoplasm Invasiveness | en_US |
dc.subject.mesh | Disease Progression | en_US |
dc.subject.mesh | Neovascularization, Pathologic | en_US |
dc.subject.mesh | GTP-Binding Proteins | en_US |
dc.subject.mesh | Oxidoreductases | en_US |
dc.subject.mesh | Transglutaminases | en_US |
dc.subject.mesh | Glutathione | en_US |
dc.subject.mesh | Chloride Channels | en_US |
dc.subject.mesh | Proteome | en_US |
dc.subject.mesh | Treatment Outcome | en_US |
dc.subject.mesh | Survival Analysis | en_US |
dc.subject.mesh | Proteomics | en_US |
dc.subject.mesh | Protein Binding | en_US |
dc.subject.mesh | Models, Biological | en_US |
dc.subject.mesh | Female | en_US |
dc.subject.mesh | Human Umbilical Vein Endothelial Cells | en_US |
dc.subject.mesh | Cancer-Associated Fibroblasts | en_US |
dc.title | Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity | en_US |
dc.type | Journal Article | |
utslib.citation.volume | 8 | en_US |
utslib.for | 0601 Biochemistry and Cell Biology | en_US |
utslib.for | MD Multidisciplinary | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Life Sciences | |
pubs.organisational-group | /University of Technology Sydney/Strength - CHT - Health Technologies | |
pubs.organisational-group | /University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices | |
utslib.copyright.status | open_access | |
pubs.publication-status | Published | en_US |
pubs.volume | 8 | en_US |
Abstract:
© The Author(s) 2017. 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.
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