Protein kinase CK2 regulates AKT, NF-κB and STAT3 activation, stem cell viability and proliferation in acute myeloid leukemia
| Autor: | Carmela Gurrieri, Alessandra Brancalion, Marilena Carrino, Elisa Mandato, Gianpietro Semenzato, L Quotti Tubi, Fortunato Zaffino, Livio Trentin, Francesco Piazza, Gianni Binotto, Paolo Macaccaro, Sabrina Manni, Ketty Gianesin, E Doriguzzi Breatta, S Canovas Nunes, Renato Zambello |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adult Male STAT3 Transcription Factor Cancer Research Cell Survival Gene Expression Leukemia inhibitory factor receptor Antineoplastic Agents Immunophenotyping 03 medical and health sciences Promyelocytic leukemia protein 0302 clinical medicine Adenosine Triphosphate Cancer stem cell hemic and lymphatic diseases Cell Line Tumor medicine Humans Casein Kinase II Protein Kinase Inhibitors Aged Cell Proliferation Aged 80 and over Polycomb Repressive Complex 1 biology Cell Cycle Forkhead Box Protein O3 NF-kappa B Myeloid leukemia Hematology Middle Aged medicine.disease Haematopoiesis Leukemia Leukemia Myeloid Acute 030104 developmental biology Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research biology.protein Neoplastic Stem Cells Female Stem cell Leukemia inhibitory factor Proto-Oncogene Proteins c-akt Biomarkers Signal Transduction |
| Zdroj: | Europe PubMed Central |
| Popis: | Protein kinase CK2 sustains acute myeloid leukemia cell growth, but its role in leukemia stem cells is largely unknown. Here, we discovered that the CK2 catalytic α and regulatory β subunits are consistently expressed in leukemia stem cells isolated from acute myeloid leukemia patients and cell lines. CK2 inactivation with the selective inhibitor CX-4945 or RNA interference induced an accumulation of leukemia stem cells in the late S-G2-M phases of the cell cycle and triggered late-onset apoptosis. As a result, leukemia stem cells displayed an increased sensitivity to the chemotherapeutic agent doxorubicin. From a molecular standpoint, CK2 blockade was associated with a downmodulation of the stem cell-regulating protein BMI-1 and a marked impairment of AKT, nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) activation, whereas FOXO3a nuclear activity was induced. Notably, combined CK2 and either NF-κB or STAT3 inhibition resulted in a superior cytotoxic effect on leukemia stem cells. This study suggests that CK2 blockade could be a rational approach to minimize the persistence of residual leukemia cells. |
| Databáze: | OpenAIRE |
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