Publication

Trail receptor gene editing unveils trail-r1 as a master player of apoptosis induced by trail and er stres

Florent, Dufour
; 
Thibault, Rattier
; 
Andrei Alexandru, Constantinescu
; 
Luciana, Zischler
; 
Aymeric, Morlé
; 
Hazem, Ben Mabrouk
; 
Etienne, Humblin
; 
Guillaume, Jacquemin
; 
Eva, Szegezdi
; 
Fabien, Delacote
... show 7 more
Identifiers
http://hdl.handle.net/10379/11285
 https://doi.org/10.13025/27883
Publication Date
2016-12-27
Keywords
receptor, trail, signaling, apoptosis, cancer, colon-cancer-cells, tumoricidal activity, selective mutants, breast-cancer, death, ligand, membrane, pathway, dr5, metastasis
Type
Article
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Citation
Florent, Dufour; Thibault, Rattier; Andrei Alexandru, Constantinescu; Luciana, Zischler; Aymeric, Morlé; Hazem, Ben Mabrouk; Etienne, Humblin; Guillaume, Jacquemin; Eva, Szegezdi; Fabien, Delacote; Naziha, Marrakchi; Gilles, Guichard; Catherine, Pellat-Deceunyn; Pierre, Vacher; Patrick, Legembre; Carmen, Garrido; Micheau, Olivier (2016). Trail receptor gene editing unveils trail-r1 as a master player of apoptosis induced by trail and er stres. Oncotarget 8 (6), 9974-9985
Abstract
TRAIL induces selective tumor cell death through TRAIL-R1 and TRAIL-R2. Despite the fact that these receptors share high structural homologies, induction of apoptosis upon ER stress, cell autonomous motility and invasion have solely been described to occur through TRAIL-R2. Using the TALEN gene-editing approach, we show that TRAIL-R1 can also induce apoptosis during unresolved unfolded protein response (UPR). Likewise, TRAIL-R1 was found to co-immunoprecipitate with FADD and caspase-8 during ER stress. Its deficiency conferred resistance to apoptosis induced by thaspigargin, tunicamycin or brefeldin A. Our data also demonstrate that tumor cell motility and invasion-induced by TRAIL-R2 is not cell autonomous but induced in a TRAIL-dependant manner. TRAIL-R1, on the other hand, is unable to trigger cell migration owing to its inability to induce an increase in calcium flux. Importantly, all the isogenic cell lines generated in this study revealed that apoptosis induced TRAIL is preferentially induced by TRAIL-R1. Taken together, our results provide novel insights into the physiological functions of TRAIL-R1 and TRAIL-R2 and suggest that targeting TRAIL-R1 for anticancer therapy is likely to be more appropriate owing to its lack of pro-motile signaling capability.
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Publisher
Impact Journals, LLC
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
cbn
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Externally hosted open access publications with University of Galway authors (2)