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Article

TRAIL Triggers CRAC-Dependent Calcium Influx and Apoptosis through the Recruitment of Autophagy Proteins to Death-Inducing Signaling Complex

1
Institut Bergonié, INSERM U1218, University of Bordeaux, 33000 Bordeaux, France
2
Lipides, Nutrition Cancer, INSERM, UMR1231, 21079 Dijon, France
3
UFR Science de Santé, Université de Bourgogne, Franche-Comté, 21079 Dijon, France
4
Centre de Recherche des Cordeliers, INSERM UMRS 1138, Sorbonne Université, Université de Paris, Equipe 11 Labellisée par la Ligue Contre le Cancer, 75006 Paris, France
5
Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France
6
Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 75015 Paris, France
7
Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran P.O. Box 14965/161, Iran
*
Authors to whom correspondence should be addressed.
Co-first authors.
Academic Editor: Ciro Isidoro
Cells 2022, 11(1), 57; https://doi.org/10.3390/cells11010057
Received: 14 November 2021 / Revised: 12 December 2021 / Accepted: 22 December 2021 / Published: 25 December 2021
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills various cancer cell types, but also leads to the activation of signaling pathways that favor resistance to cell death. Here, we investigated the as yet unknown roles of calcium signaling and autophagy regulatory proteins during TRAIL-induced cell death in leukemia cells. Taking advantage of the Gene Expression Profiling Interactive Analysis (GEPIA) project, we first found that leukemia patients present a unique TRAIL receptor gene expression pattern that may reflect their resistance to TRAIL. The exposure of NB4 acute promyelocytic leukemia cells to TRAIL induces intracellular Ca2+ influx through a calcium release-activated channel (CRAC)-dependent mechanism, leading to an anti-apoptotic response. Mechanistically, we showed that upon TRAIL treatment, two autophagy proteins, ATG7 and p62/SQSTM1, are recruited to the death-inducing signaling complex (DISC) and are essential for TRAIL-induced Ca2+ influx and cell death. Importantly, the treatment of NB4 cells with all-trans retinoic acid (ATRA) led to the upregulation of p62/SQSTM1 and caspase-8 and, when added prior to TRAIL stimulation, significantly enhanced DISC formation and the apoptosis induced by TRAIL. In addition to uncovering new pleiotropic roles for autophagy proteins in controlling the calcium response and apoptosis triggered by TRAIL, our results point to novel therapeutic strategies for sensitizing leukemia cells to TRAIL. View Full-Text
Keywords: ATRA; ATG7; autophagy; cancer; CRAC channels; DISC; leukemia; ORAI1; p62/SQSTM1; resistance to therapy ATRA; ATG7; autophagy; cancer; CRAC channels; DISC; leukemia; ORAI1; p62/SQSTM1; resistance to therapy
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MDPI and ACS Style

Airiau, K.; Vacher, P.; Micheau, O.; Prouzet-Mauleon, V.; Kroemer, G.; Moosavi, M.A.; Djavaheri-Mergny, M. TRAIL Triggers CRAC-Dependent Calcium Influx and Apoptosis through the Recruitment of Autophagy Proteins to Death-Inducing Signaling Complex. Cells 2022, 11, 57. https://doi.org/10.3390/cells11010057

AMA Style

Airiau K, Vacher P, Micheau O, Prouzet-Mauleon V, Kroemer G, Moosavi MA, Djavaheri-Mergny M. TRAIL Triggers CRAC-Dependent Calcium Influx and Apoptosis through the Recruitment of Autophagy Proteins to Death-Inducing Signaling Complex. Cells. 2022; 11(1):57. https://doi.org/10.3390/cells11010057

Chicago/Turabian Style

Airiau, Kelly, Pierre Vacher, Olivier Micheau, Valerie Prouzet-Mauleon, Guido Kroemer, Mohammad A. Moosavi, and Mojgan Djavaheri-Mergny. 2022. "TRAIL Triggers CRAC-Dependent Calcium Influx and Apoptosis through the Recruitment of Autophagy Proteins to Death-Inducing Signaling Complex" Cells 11, no. 1: 57. https://doi.org/10.3390/cells11010057

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