Nuclear localization of the CK2α-subunit correlates with poor prognosis in Clear Cell Renal Cell Carcinoma

Maj Rabjerg*, Barbara Guerra, Aida Oliván-Viguera, Minne Line Nedergaard Mikkelsen, Ralf Köhler, Olaf Georg Issinger, Niels Marcussen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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.

Original languageEnglish
JournalOncotarget
Volume8
Issue number1
Pages (from-to)1613-1627
ISSN1949-2553
DOIs
Publication statusPublished - 3. Jan 2017

Keywords

  • CK2 subunits
  • CK2-targeted therapy
  • CX-4945
  • Protein kinase CK2
  • Renal cancer
  • Cell Movement/genetics
  • Kidney Neoplasms/mortality
  • Casein Kinase II/antagonists & inhibitors
  • Humans
  • Middle Aged
  • Carcinoma, Renal Cell/mortality
  • Male
  • RNA, Messenger/genetics
  • Biomarkers, Tumor/genetics
  • Neoplasm Invasiveness/genetics
  • Adenoma, Oxyphilic/mortality
  • Aged, 80 and over
  • Cell Line, Tumor
  • Adult
  • Cell Proliferation/genetics
  • Female
  • Aged
  • Naphthyridines/pharmacology

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