RT info:eu-repo/semantics/article
T1 Secreted CLIC3 drives cancer progression through its glutathione-dependent oxidoreductase activity
A1 Hernández Fernaud, Juan Ramón
A1 Ruengeler, Elena
A1 Casazza, Andrea
A1 Neilson, Lisa J.
A1 Pulleine, Ellie
A1 Santi, Alice
A1 Ismail, Shehab
A1 Lilla, Sergio
A1 Dhayade, Sandeep
A1 MacPherson, Iain R.
A1 McNeish, Iain
A1 Ennis, Darren
A1 Ali, Hala
A1 Kugeratski, Fernanda G.
A1 Al Khamici, Heba
A1 Biggelaar, Maartje van den
A1 Berghe, Peter V.E. van den
A1 Cloix, Catherine
A1 McDonald, Laura
A1 Millan, David
A1 Hoyle, Aoisha
A1 Kuchnio, Anna
A1 Carmeliet, Peter
A1 Valenzuela, Stella M.
A1 Blyth, Karen
A1 Yin, Huabing
A1 Mazzone, Massimiliano
A1 Norman, Jim C.
A1 Zanivan, Sara
A2 BioquímicaMicrobiología, Biología Celular y Genética
A2 The Beatson Institute for Cancer ResearchGlasgow, UK
AB 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.
YR 2016
FD 2016
LK http://riull.ull.es/xmlui/handle/915/38873
UL http://riull.ull.es/xmlui/handle/915/38873
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 31-oct-2024