Aberrant signalling by protein kinase CK2 in imatinib-resistant chronic myeloid leukaemia cells: Biochemical evidence and therapeutic perspectives (Articolo in rivista)

Type
Label
  • Aberrant signalling by protein kinase CK2 in imatinib-resistant chronic myeloid leukaemia cells: Biochemical evidence and therapeutic perspectives (Articolo in rivista) (literal)
Anno
  • 2013-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.molonc.2013.08.006 (literal)
Alternative label
  • Borgo C.; Cesaro L.; Salizzato V.; Ruzzene M.; Massimino M.L.; Pinna L.A.; Donella-Deana A. (2013)
    Aberrant signalling by protein kinase CK2 in imatinib-resistant chronic myeloid leukaemia cells: Biochemical evidence and therapeutic perspectives
    in Molecular oncology (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Borgo C.; Cesaro L.; Salizzato V.; Ruzzene M.; Massimino M.L.; Pinna L.A.; Donella-Deana A. (literal)
Pagina inizio
  • 1103 (literal)
Pagina fine
  • 1115 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url
  • http://www.scopus.com/inward/record.url?eid=2-s2.0-84887869270&partnerID=q2rCbXpz (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 7 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 6 (literal)
Note
  • Scopu (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Biomedical Sciences, University of Padova, CNR Neuroscience Institute, Viale G. Colombo 3, 35131 Padova, Italy (literal)
Titolo
  • Aberrant signalling by protein kinase CK2 in imatinib-resistant chronic myeloid leukaemia cells: Biochemical evidence and therapeutic perspectives (literal)
Abstract
  • Chronic myeloid leukaemia (CML) is driven by the fusion protein Bcr-Abl, a constitutively active tyrosine kinase playing a crucial role in initiation and maintenance of CML phenotype. Despite the great efficacy of the Bcr-Abl-specific inhibitor imatinib, resistance to this drug is recognized as a major problem in CML treatment. We found that in LAMA84 cells, characterized by imatinib-resistance caused by BCR-ABL1 gene amplification, the pro-survival protein kinase CK2 is up-regulated as compared to the sensitive cells. CK2 exhibits a higher protein-level and a parallel enhancement of catalytic activity. Consistently, CK2-catalysed phosphorylation of Akt-Ser129 is increased. CK2 co-localizes with Bcr-Abl in the cytoplasmic fraction as judged by subcellular fractionation and fluorescence immunolocalization. CK2 and Bcr-Abl are members of the same multi-protein complex(es) in imatinib-resistant cells as demonstrated by co-immunoprecipitation and co-sedimentation in glycerol gradients. Cell treatment with CX-4945, a CK2 inhibitor currently in clinical trials, counteracts CK2/Bcr-Abl interaction and causes cell death by apoptosis. Interestingly, combination of CX-4945 with imatinib displays a synergistic effect in reducing cell viability. Consistently, knockdown of CK2? expression by siRNA restores the sensitivity of resistant LAMA84 cells to low imatinib concentrations. Remarkably, the CK2/Bcr-Abl interaction and the sensitization towards imatinib obtained by CK2-inhibition in LAMA84 is observable also in other imatinib-resistant CML cell lines. These results demonstrate that CK2 contributes to strengthen the imatinib-resistance phenotype of CML cells conferring survival advantage against imatinib. We suggest that CK2 inhibition might be a promising tool for combined strategies in CML therapy. © 2013 Federation of European Biochemical Societies. (literal)
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