RT Journal Article
T1 Negative regulation of urokinase receptor activity by a GPI-specific phospholipase C in breast cancer cells
A1 van Veen, Michiel
A1 Matas-Rico, Elisa
A1 van de Wetering, Koen
A1 Leyton-Puig, Daniela
A1 Kedziora, Katarzyna M
A1 De Lorenzi, Valentina
A1 Stijf-Bultsma, Yvette
A1 van den Broek, Bram
A1 Jalink, Kees
A1 Sidenius, Nicolai
A1 Perrakis, Anastassis
A1 Moolenaar, Wouter H
K1 Receptores celulares
K1 Citología
AB The urokinase receptor (uPAR) is a glycosylphosphatidylinositol (GPI)-anchored protein that promotes tissue remodeling, tumor cell adhesion, migration and invasion. uPAR mediates degradation of the extracellular matrix through protease recruitment and enhances cell adhesion, migration and signaling through vitronectin binding and interactions with integrins. Full-length uPAR is released from the cell surface, but the mechanism and significance of uPAR shedding remain obscure. Here we identify transmembrane glycerophosphodiesterase GDE3 as a GPI-specific phospholipase C that cleaves and releases uPAR with consequent loss of function, whereas its homologue GDE2 fails to attack uPAR. GDE3 overexpression depletes uPAR from distinct basolateral membrane domains in breast cancer cells, resulting in a less transformed phenotype, it slows tumor growth in a xenograft model and correlates with prolonged survival in patients. Our results establish GDE3 as a negative regulator of the uPAR signaling network and, furthermore, highlight GPI-anchor hydrolysis as a cell-intrinsic mechanism to alter cell behavior.
PB Elife
YR 2017
FD 2017-08-29
LK https://hdl.handle.net/10630/33645
UL https://hdl.handle.net/10630/33645
LA eng
NO Michiel van VeenElisa Matas-RicoKoen van de WeteringDaniela Leyton-PuigKatarzyna M KedzioraValentina De LorenziYvette Stijf-BultsmaBram van den BroekKees JalinkNicolai SideniusAnastassis PerrakisWouter H Moolenaar (2017) Negative regulation of urokinase receptor activity by a GPI-specific phospholipase C in breast cancer cells eLife 6:e23649.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026