title: Nuclear localization of the CK2α-subunit correlates with poor prognosis in clear cell renal cell carcinoma.
abstract: Protein kinase CK2α, one of the two catalytic isoforms of the protein kinase CK2 has been shown to contribute to tumor development, tumor proliferation and suppression of apoptosis in various malignancies. We conducted this study to investigate CK2 expression in different subtypes of Renal Cell Carcinoma (RCC) and in the benign oncocytoma. qRT-PCR, immunohistochemistry and Western blot analyses revealed that CK2α expression was significantly increased at the mRNA and protein levels in clear cell RCC (ccRCC). Also the kinase activity of CK2 was significantly increased in ccRCC compared to normal renal cortex. Nuclear protein expression of CK2α correlated in univariate analysis with poor Progression Free Survival (HR = 8.11, p = 0.016). Functional analyses (cell proliferation assay) revealed an inhibitory effect of Caki-2 cell growth following CK2 inhibition with CX-4945. Our results suggest that CK2α promotes migration and invasion of ccRCC and therefore could serve as a novel prognostic biomarker and molecular therapeutic target in this type of cancer.
authors.affiliation: Department of Pathology, Odense University Hospital, DK-5000 Odense, Denmark.
authors.forename: Maj
authors.initials: M
authors.lastname: Rabjerg
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors.forename: Barbara
authors.initials: B
authors.lastname: Guerra
authors.affiliation: Aragon Agency for Research and Development (ARAID), IACS, IIS Aragon, 50009 Zaragoza, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Oliván-Viguera
authors.affiliation: Department of Pathology, Odense University Hospital, DK-5000 Odense, Denmark.
authors.forename: Minne Line Nedergaard
authors.initials: ML
authors.lastname: Mikkelsen
authors.affiliation: Aragon Agency for Research and Development (ARAID), IACS, IIS Aragon, 50009 Zaragoza, Spain.
authors.forename: Ralf
authors.initials: R
authors.lastname: Köhler
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense, Denmark.
authors.forename: Olaf-Georg
authors.initials: OG
authors.lastname: Issinger
authors.affiliation: Department of Pathology, Odense University Hospital, DK-5000 Odense, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Marcussen
mesh_terms: D018249:Adenoma, Oxyphilic / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000494:pharmacology; D009361:Neoplasm Invasiveness / Q000235:genetics; D010619:Phenazines; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D009287:Naphthyridines; D010619:Phenazines; D012333:RNA, Messenger; C555142:silmitasertib; D047390:Casein Kinase II
keywords: CK2 subunits; CK2-targeted therapy; CX-4945; protein kinase CK2; renal cancer