Optimal interleukin-7 receptor-mediated signaling, cell cycle progression and viability of T-cell acute lymphoblastic leukemia cells rely on casein kinase 2 activity
| Autor: | Bruno A. Cardoso, João T. Barata, Alice Melão, Maureen Spit |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cell Survival Biology Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Article Interleukin-7 Receptor alpha Subunit 03 medical and health sciences Downregulation and upregulation medicine Humans Interleukin-7 receptor Protein kinase A Casein Kinase II Cells Cultured Cell growth Interleukin-7 Cell Cycle Hematology Cell cycle medicine.disease Cell biology Leukemia 030104 developmental biology HEK293 Cells Casein kinase 2 Signal transduction Signal Transduction |
| Zdroj: | Haematologica |
| ISSN: | 0390-6078 |
| DOI: | 10.3324/haematol.2015.141143 |
| Popis: | Interleukin-7 and interleukin-7 receptor are essential for normal T-cell development and homeostasis, whereas excessive interleukin-7/interleukin-7 receptor-mediated signaling promotes leukemogenesis. The protein kinase, casein kinase 2, is overexpressed and hyperactivated in cancer, including T-cell acute lymphoblastic leukemia. Herein, we show that while interleukin-7 had a minor but significant positive effect on casein kinase 2 activity in leukemia T-cells, casein kinase 2 activity was mandatory for optimal interleukin-7/interleukin-7 receptor-mediated signaling. Casein kinase 2 pharmacological inhibition impaired signal transducer and activator of transcription 5 and phosphoinositide 3-kinase/v-Akt murine thymoma viral oncogene homolog 1 pathway activation triggered by interleukin-7 or by mutational activation of interleukin-7 receptor. By contrast, forced expression of casein kinase 2 augmented interleukin-7 signaling in human embryonic kidney 293T cells reconstituted with the interleukin-7 receptor machinery. Casein kinase 2 inactivation prevented interleukin-7-induced B-cell lymphoma 2 upregulation, maintenance of mitochondrial homeostasis and viability of T-cell acute lymphoblastic leukemia cell lines and primary leukemia cells collected from patients at diagnosis. Casein kinase 2 inhibition further abrogated interleukin-7-mediated cell growth and upregulation of the transferrin receptor, and blocked cyclin A and E upregulation and cell cycle progression. Notably, casein kinase 2 was also required for the viability of mutant interleukin-7 receptor expressing leukemia T-cells. Overall, our study identifies casein kinase 2 as a major player in the effects of interleukin-7 and interleukin-7 receptor in T-cell acute lymphoblastic leukemia. This further highlights the potential relevance of targeting casein kinase 2 in this malignancy. |
| Databáze: | OpenAIRE |
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