Nuclear localization of the CK2α-subunit correlates with poor prognosis in clear cell renal cell carcinoma

Oncotarget. 2017 Jan 3;8(1):1613-1627. doi: 10.18632/oncotarget.13693.

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.

Keywords: CK2 subunits; CK2-targeted therapy; CX-4945; protein kinase CK2; renal cancer.

MeSH terms

  • Adenoma, Oxyphilic / mortality
  • Adenoma, Oxyphilic / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology*
  • Casein Kinase II / antagonists & inhibitors
  • Casein Kinase II / genetics*
  • Casein Kinase II / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Humans
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology*
  • Male
  • Middle Aged
  • Naphthyridines / pharmacology
  • Neoplasm Invasiveness / genetics
  • Phenazines
  • RNA, Messenger / genetics

Substances

  • Biomarkers, Tumor
  • Naphthyridines
  • Phenazines
  • RNA, Messenger
  • silmitasertib
  • Casein Kinase II

Supplementary concepts

  • Oncocytoma, renal