Research Papers:

Under-expression of CK2β subunit in ccRCC represents a complementary biomarker of p-STAT3 Ser727 that correlates with patient survival

Jordi Vilardell, Estefania Alcaraz, Eduard Sarró, Enric Trilla, Thaïs Cuadros, Inés de Torres, Maria Plana, Santiago Ramón y Cajal, Lorenzo A. Pinna, Maria Ruzzene, Juan Morote, Anna Meseguer _ and Emilio Itarte

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Oncotarget. 2018; 9:5736-5751. https://doi.org/10.18632/oncotarget.23422

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Jordi Vilardell1,*, Estefania Alcaraz1,*, Eduard Sarró2, Enric Trilla3, Thaïs Cuadros2, Inés de Torres4, Maria Plana1,5, Santiago Ramón y Cajal4,6, Lorenzo A. Pinna7, Maria Ruzzene7, Juan Morote3, Anna Meseguer2,8,9,10,# and Emilio Itarte1,5,#

1Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain

2Fisiopatología Renal, CIBBIM, VHIR, Barcelona, Spain

3Servicio de Urología, Hospital Vall d’Hebrón, Barcelona, Spain

4Servicio de Anatomía Patológica, Hospital Vall d’Hebrón, Barcelona, Spain

5Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain

6Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Barcelona, Spain

7Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padova, Padova, Italy

8Departament de Bioquimica i Biologia Molecular, Unitat de Bioquímica de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain

9Instituto Reina Sofía de Investigación Nefrológica, Fundación Renal Íñigo Álvarez de Toledo, Madrid, Spain

10Red de Investigación Renal (REDINREN), Barcelona, Spain

*These authors contributed equally to this work


Correspondence to:

Anna Meseguer, email: [email protected]

Emilio Itarte, email: [email protected]

Keywords: protein kinase CK2; clear cell renal cell carcinoma (ccRCC); epithelial-to-mesenchymal transition (EMT); STAT3; patient outcome

Received: March 22, 2017     Accepted: December 13, 2017     Published: December 19, 2017


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 CK2β (CK2βcyt) levels in the more advanced tumors. Stable downregulation of CK2β 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, CK2β was required in order to observe STAT3 Ser727 phosphorylation in HK-2 but not in 786-O cells.

We also observed that CK2β improved the prognostic value of p-STAT3 Ser727, as CK2βcyt>41 (median value) discriminates patients free of disease for a period of 10 years upon surgery, from those with CK2βcyt<41, when p-STAT3 Ser727levels are low.

We conclude that CK2β down-regulation might represent a mechanism to support EMT and angiogenesis and that CK2βcyt levels are instrumental to refine prognosis of ccRCC patients with low p-STAT3 Ser727 levels.

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