title: Identification of a novel crosstalk between casein kinase 2α and NPM-ALK in ALK-positive anaplastic large cell lymphoma.
abstract: It was previously reported that β-catenin contributes to the tumorigenesis of ALK-positive anaplastic large cell lymphoma (ALK(+)ALCL), and the oncogenic effects of β-catenin in these tumors are promoted by NPM-ALK, an abnormal fusion protein characteristic of ALK(+)ALCL. In this study, we hypothesized that NPM-ALK promotes the oncogenic activity of β-catenin via its functional interactions with the Wnt canonical pathway (WCP). To test this hypothesis, we examined if NPM-ALK modulates the gene expression of various members in the WCP. Using a Wnt pathway-specific oligonucleotide array and Western blots, we found that the expression of casein kinase 2α (CK2α) was substantially downregulated in ALK(+)ALCL cells in response to siRNA knockdown of NPM-ALK. CK2α is biologically important in ALK(+)ALCL, as its inhibition using 4,5,6,7-tetrabromobenzotriazole or siRNA resulted in a significant decrease in cell growth and a substantial decrease in the β-catenin protein level. Furthermore, CK2α co-immunoprecipitated with NPM-ALK and regulated its level of serine phosphorylation, a feature previously shown to correlate with the oncogenic potential of this fusion protein. To conclude, this study has revealed a novel crosstalk between NPM-ALK and CK2α, and our data supports the model that these two molecules work synergistically to promote the tumorigenicity of these lymphomas.
authors.affiliation: Department of Laboratory Medicine and Pathology, Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Hanan
authors.initials: H
authors.lastname: Armanious
authors.forename: Pascal
authors.initials: P
authors.lastname: Gelebart
authors.forename: Mona
authors.initials: M
authors.lastname: Anand
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014230:Triazoles / Q000494:pharmacology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C405354:4,5,6,7-tetrabromobenzotriazole; D004791:Enzyme Inhibitors; D034741:RNA, Small Interfering; D014230:Triazoles; D051153:Wnt Proteins; D051176:beta Catenin; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases; D047390:Casein Kinase II