Under-expression of CK2ß subunit in ccRCC represents a complementary biomarker of p-STAT3 Ser727 that correlates with patient survival.

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of renal cancer. STAT3 pathway is altered in these tumors and p-STAT3 Ser727 is an independent prognostic factor for ccRCC. Protein kinase CK2 is altered in different types of tumors and overexpression of CK2α is considered predictive of bad prognosis and metastatic risk. CK2 subunits analyses in ccRCC samples showed increased CK2α/α' nuclear content in all cases, but decreased cytosolic CK2ß (CK2ßcyt) levels in the more advanced tumors. Stable downregulation of CK2ß in renal proximal tubular (HK-2) and clear cell adenocarcinoma (786-O) cells triggered changes in E-cadherin, vimentin and Snail1 protein levels indicative of epithelial-to-mesenchymal transition (EMT), and increased HIF-α. Moreover, CK2ß was required in order to observe STAT3 Ser727 phosphorylation in HK-2 but not in 786-O cells. We also observed that CK2ß improved the prognostic value of p-STAT3 Ser727, as CK2ßcyt>41 (median value) discriminates patients free of disease for a period of 10 years upon surgery, from those with CK2ßcyt<41, when p-STAT3 Ser727levels are low. We conclude that CK2ß down-regulation might represent a mechanism to support EMT and angiogenesis and that CK2ßcyt levels are instrumental to refine prognosis of ccRCC patients with low p-STAT3 Ser727 levels.