Involvement of ORAI1/SOCE in Human AML Cell Lines and Primary Cells According to ABCB1 Activity, LSC Compartment and Potential Resistance to Ara-C Exposure
| Autor: | Clara Lewuillon, Aurélie Guillemette, Sofia Titah, Faruk Shaik, Nathalie Jouy, Ossama Labiad, Valerio Farfariello, Marie-Océane Laguillaumie, Thierry Idziorek, Adeline Barthélémy, Pauline Peyrouze, Céline Berthon, Mehmet Tarhan, Meyling Cheok, Bruno Quesnel, Loïc Lemonnier, Yasmine Touil |
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| Přispěvatelé: | University of Lille, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Integrated Micro Mechatronics Systems (LIMMS), The University of Tokyo (UTokyo)-Centre National de la Recherche Scientifique (CNRS), Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Plateforme BioImaging Center Lille (BICeL), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, CHU Lille, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Faculté de Médecine Henri Warembourg - Université de Lille, Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Bio-Micro-Electro-Mechanical Systems - IEMN (BIOMEMS - IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), JUNIA (JUNIA), Université catholique de Lille (UCL), This research was funded by grants from Contrat de Plan Etat-Région CPER Cancer 2015–2020, INSERM, CNRS, Ligue contre le cancer (Septentrion), Ligue nationale contre le cancer, Fondation ARC, the University of Lille and the Institut de Recherche sur le Cancer de Lille (IRCL). C.L. and M.-O.L. are financed by Lille Hospital and by the Hauts de France Region. F.A.S. is financed by the Institut de Recherche sur Le Cancer de Lille (IRCL)., We would also like to thank Emilie Floquet and Pascaline Segard for their technical assistance., IEMN, Collection |
| Rok vydání: | 2022 |
| Předmět: |
NFAT
ATP Binding Cassette Transporter Subfamily B ORAI1 Protein [SPI] Engineering Sciences [physics] Ara-C leukemic stem cells Catalysis Cell Line Inorganic Chemistry [SPI]Engineering Sciences [physics] AML calcium SOCE ORAI1 ABCB1 Humans Calcium Signaling Stromal Interaction Molecule 1 Physical and Theoretical Chemistry Molecular Biology Spectroscopy Organic Chemistry Cytarabine General Medicine Computer Science Applications Leukemia Myeloid Acute Calcium |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, 2022, 23 (10), pp.5555. ⟨10.3390/ijms23105555⟩ International Journal of Molecular Sciences; Volume 23; Issue 10; Pages: 5555 |
| ISSN: | 1422-0067 1661-6596 |
| DOI: | 10.3390/ijms23105555 |
| Popis: | International audience; Acute myeloid leukemia (AML) is a hematological malignancy with a high risk of relapse. This issue is associated with the development of mechanisms leading to drug resistance that are not yet fully understood. In this context, we previously showed the clinical significance of the ATP binding cassette subfamily B-member 1 (ABCB1) in AML patients, namely its association with stemness markers and an overall worth prognosis. Calcium signaling dysregulations affect numerous cellular functions and are associated with the development of the hallmarks of cancer. However, in AML, calcium-dependent signaling pathways remain poorly investigated. With this study, we show the involvement of the ORAI1 calcium channel in store-operated calcium entry (SOCE), the main calcium entry pathway in non-excitable cells, in two representative human AML cell lines (KG1 and U937) and in primary cells isolated from patients. Moreover, our data suggest that in these models, SOCE varies according to the differentiation status, ABCB1 activity level and leukemic stem cell (LSC) proportion. Finally, we present evidence that ORAI1 expression and SOCE amplitude are modulated during the establishment of an apoptosis resistance phenotype elicited by the chemotherapeutic drug Ara-C. Our results therefore suggest ORAI1/SOCE as potential markers of AML progression and drug resistance apparition. |
| Databáze: | OpenAIRE |
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