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dc.contributor.authorCabanas, Hélène
dc.contributor.authorHarnois, Thomas
dc.contributor.authorMagaud, Christophe
dc.contributor.authorCousin, Laëtitia
dc.contributor.authorConstantin, Bruno
dc.contributor.authorBourmeyster, Nicolas
dc.contributor.authorDéliot, Nadine
dc.date.accessioned2019-11-25T04:44:42Z
dc.date.available2019-11-25T04:44:42Z
dc.date.issued2018
dc.identifier.issn1949-2553
dc.identifier.doi10.18632/oncotarget.25241
dc.identifier.urihttp://hdl.handle.net/10072/389248
dc.description.abstractBackground: Chronic myeloid leukemia (CML) results from hematopoietic stem cell transformation by the bcr-abl chimeric oncogene, encoding a 210 kDa protein with constitutive tyrosine kinase activity. In spite of the efficiency of tyrosine kinase inhibitors (TKI; Imatinib), other strategies are explored to eliminate CML leukemia stem cells, such as calcium pathways. Results: In this work, we showed that Store-Operated Calcium Entry (SOCE) and thrombin induced calcium influx were decreased in Bcr-Abl expressing 32d cells (32d-p210). The 32d-p210 cells showed modified Orai1/STIM1 ratio and reduced TRPC1 expression that could explain SOCE reduction. Decrease in SOCE and thrombin induced calcium entry was associated to reduced Nuclear Factor of Activated T cells (NFAT) nucleus translocation in 32d-p210 cells. We demonstrated that SOCE blockers enhanced cell mobility of 32d-p210 cells and reduced the proliferation rate in both 32d cell lines. TKI treatment slightly reduced the thrombin-induced response, but imatinib restored SOCE to the wild type level. Bcr-Abl is also known to deregulate Protein Kinase C (PKC), which was described to modulate calcium entries. We showed that PKC enhances SOCE and thrombin induced calcium entries in control cells while this effect is lost in Bcr-Abl-expressing cells. Conclusion: The tyrosine kinase activity seems to regulate calcium entries probably not directly but through a global cellular reorganization involving a PKC pathway. Altogether, calcium entries are deregulated in Bcr-Abl-expressing cells and could represent an interesting therapeutic target in combination with TKI.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherImpact Journals, LLC
dc.publisher.placeUnited States
dc.relation.ispartofpagefrom26309
dc.relation.ispartofpageto26327
dc.relation.ispartofissue41
dc.relation.ispartofjournalOncotarget
dc.relation.ispartofvolume9
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchcode1112
dc.titleDeregulation of calcium homeostasis in Bcr-Abl-dependent chronic myeloid leukemia
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationCabanas, H; Harnois, T; Magaud, C; Cousin, L; Constantin, B; Bourmeyster, N; Déliot, N, Deregulation of calcium homeostasis in Bcr-Abl-dependent chronic myeloid leukemia, Oncotarget, 2018, 9 (41), pp. 26309-26327
dcterms.licensehttps://creativecommons.org/licenses/by/3.0/
dc.date.updated2019-11-21T01:08:13Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© Cabanas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
gro.hasfulltextFull Text
gro.griffith.authorCabanas, Helene


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