Targeting CAMKK2 and SOC Channels as a Novel Therapeutic Approach for Sensitizing Acute Promyelocytic Leukemia Cells to All-Trans Retinoic Acid
dc.contributor.author | Merhi, Faten | |
dc.contributor.author | Alvarez-Valadez, Karla | |
dc.contributor.author | Trepiana Arin, Jenifer | |
dc.contributor.author | Lescoat, Claire | |
dc.contributor.author | Groppi, Alexis | |
dc.contributor.author | Dupuy, Jean-William | |
dc.contributor.author | Soubeyran, Pierre | |
dc.contributor.author | Kroemer, Guido | |
dc.contributor.author | Vacher, Pierre | |
dc.contributor.author | Djavaheri-Mergny, Mojgan | |
dc.date.accessioned | 2021-12-28T10:09:25Z | |
dc.date.available | 2021-12-28T10:09:25Z | |
dc.date.issued | 2021-11-30 | |
dc.identifier.citation | Cells 10(12) : (2021) // Article ID 3364 | es_ES |
dc.identifier.issn | 2073-4409 | |
dc.identifier.uri | http://hdl.handle.net/10810/54752 | |
dc.description.abstract | Calcium ions (Ca2+) play important and diverse roles in the regulation of autophagy, cell death and differentiation. Here, we investigated the impact of Ca2+ in regulating acute promyelocytic leukemia (APL) cell fate in response to the anti-cancer agent all-trans retinoic acid (ATRA). We observed that ATRA promotes calcium entry through store-operated calcium (SOC) channels into acute promyelocytic leukemia (APL) cells. This response is associated with changes in the expression profiles of ORAI1 and STIM1, two proteins involved in SOC channels activation, as well as with a significant upregulation of several key proteins associated to calcium signaling. Moreover, ATRA treatment of APL cells led to a significant activation of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and its downstream effector AMP-activated protein kinase (AMPK), linking Ca2+ signaling to autophagy. Pharmacological inhibition of SOC channels and CAMKK2 enhanced ATRA-induced cell differentiation and death. Altogether, our results unravel an ATRA-elicited signaling pathway that involves SOC channels/CAMKK2 activation, induction of autophagy, inhibition of cellular differentiation and suppression of cell death. We suggest that SOC channels and CAMKK2 may constitute novel drug targets for potentiating the anti-cancer effect of ATRA in APL patients | es_ES |
dc.description.sponsorship | F.M. was supported by a postdoctoral fellowship from the “Aquitaine Regional Council” (to MDM). K.A.-V. is supported by the Mexican National Council of Science and Technology (CONACYT, funding #757821). This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale (INSERM), a grant from SIRIC BRIO (to M.D.M.), Federation de recherche Transbiomed (to M.D-M.) and contributes to the IdEx Université de Paris ANR-18-IDEX-0001. GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR)—Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Ruban Rose”; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); Gustave Roussy Odyssea, the European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); the Leducq Foundation; a Cancer Research ASPIRE Award from the Mark Foundation; the RHU Torino Lumière; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | |
dc.subject | differentiation | es_ES |
dc.subject | cell death | es_ES |
dc.subject | autophagy | es_ES |
dc.subject | cancer | es_ES |
dc.subject | ORAI1 | es_ES |
dc.subject | STIM1 | es_ES |
dc.subject | AMPK | es_ES |
dc.subject | therapy | es_ES |
dc.subject | resistance to therapy | es_ES |
dc.title | Targeting CAMKK2 and SOC Channels as a Novel Therapeutic Approach for Sensitizing Acute Promyelocytic Leukemia Cells to All-Trans Retinoic Acid | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.date.updated | 2021-12-23T15:06:36Z | |
dc.rights.holder | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | es_ES |
dc.relation.publisherversion | https://www.mdpi.com/2073-4409/10/12/3364 | es_ES |
dc.identifier.doi | 10.3390/cells10123364 | |
dc.departamentoes | Farmacia y ciencias de los alimentos | |
dc.departamentoeu | Farmazia eta elikagaien zientziak |
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Except where otherwise noted, this item's license is described as © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).