Chemotherapy overcomes TRAIL-R4-mediated TRAIL resistance at the DISC level
| Autor: | Morizot, Alexandre, Mérino, Delphine, Lalaoui, Najoua, Jacquemin, Guillaume, Granci, Virginie, Iessi, Elisabetta, Lanneau, David, Bouyer, Florence, Solary, Eric, Chauffert, Bruno, Saas, Philippe, Garrido, Carmen, Micheau, Olivier |
|---|---|
| Přispěvatelé: | Micheau, Olivier, Programme 'Jeunes chercheuses et jeunes chercheurs' - TRAIL et chimiothérapies anticancéreuses - - TRAILCHIM2006 - ANR-06-JCJC-0103 - JCJC - VALID, Apoptrain, Marie Curie RTN - INCOMING, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Hématopoïèse normale et pathologique, Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), INCa (Polynom174), ANR-06-JCJC-0103,TRAILCHIM,TRAIL et chimiothérapies anticancéreuses(2006), European Project |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
MESH: CASP8 and FADD-Like Apoptosis Regulating Protein
MESH: Cell Line Tumor MESH: Humans MESH: Apoptosis MESH: RNA Interference MESH: Models Biological TRAIL chemotherapy MESH: Tumor Necrosis Factor Decoy Receptors MESH: Caspase 8 MESH: Drug Resistance Neoplasm MESH: Antineoplastic Combined Chemotherapy Protocols MESH: RNA Small Interfering [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology cancer MESH: Neoplasms [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Receptors TNF-Related Apoptosis-Inducing Ligand MESH: GPI-Linked Proteins MESH: TNF-Related Apoptosis-Inducing Ligand MESH: Death Domain Receptor Signaling Adaptor Proteins |
| Zdroj: | Cell Death and Differentiation Cell Death and Differentiation, 2011, 18 (4), pp.700-11. ⟨10.1038/cdd.2010.144⟩ |
| ISSN: | 1350-9047 1476-5403 |
| DOI: | 10.1038/cdd.2010.144⟩ |
| Popis: | International audience; TNF-related apoptosis-inducing ligand or Apo2L (Apo2L/TRAIL) is a promising anti-cancer drug owing to its ability to trigger apoptosis by binding to TRAIL-R1 or TRAIL-R2, two membrane-bound receptors that are often expressed by tumor cells. TRAIL can also bind non-functional receptors such as TRAIL-R4, but controversies still exist regarding their potential to inhibit TRAIL-induced apoptosis. We show here that TRAIL-R4, expressed either endogenously or ectopically, inhibits TRAIL-induced apoptosis. Interestingly, the combination of chemotherapeutic drugs with TRAIL restores tumor cell sensitivity to apoptosis in TRAIL-R4-expressing cells. This sensitization, which mainly occurs at the death-inducing signaling complex (DISC) level, through enhanced caspase-8 recruitment and activation, is compromised by c-FLIP expression and is independent of the mitochondria. Importantly, TRAIL-R4 expression prevents TRAIL-induced tumor regression in nude mice, but tumor regression induced by TRAIL can be restored with chemotherapy. Our results clearly support a negative regulatory function for TRAIL-R4 in controlling TRAIL signaling, and unveil the ability of TRAIL-R4 to cooperate with c-FLIP to inhibit TRAIL-induced cell death. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|