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

Autor:	Vilardell J; Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain., Alcaraz E; Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain., Sarró E; Fisiopatología Renal, CIBBIM, VHIR, Barcelona, Spain., Trilla E; Servicio de Urología, Hospital Vall d'Hebrón, Barcelona, Spain., Cuadros T; Fisiopatología Renal, CIBBIM, VHIR, Barcelona, Spain., de Torres I; Servicio de Anatomía Patológica, Hospital Vall d'Hebrón, Barcelona, Spain., Plana M; Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain., Ramón Y Cajal S; Servicio de Anatomía Patológica, Hospital Vall d'Hebrón, Barcelona, Spain.; Spanish Biomedical Research Network Centre in Oncology (CIBERONC), Barcelona, Spain., Pinna LA; Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padova, Padova, Italy., Ruzzene M; Department of Biomedical Sciences and CNR Institute of Neuroscience, University of Padova, Padova, Italy., Morote J; Servicio de Urología, Hospital Vall d'Hebrón, Barcelona, Spain., Meseguer A; Fisiopatología Renal, CIBBIM, VHIR, Barcelona, Spain.; Departament de Bioquimica i Biologia Molecular, Unitat de Bioquímica de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.; Instituto Reina Sofía de Investigación Nefrológica, Fundación Renal Íñigo Álvarez de Toledo, Madrid, Spain.; Red de Investigación Renal (REDINREN), Barcelona, Spain., Itarte E; Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.; Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 Dec 19; Vol. 9 (5), pp. 5736-5751. Date of Electronic Publication: 2017 Dec 19 (Print Publication: 2018).
DOI:	10.18632/oncotarget.23422
Abstrakt:	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. Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.
Databáze:	MEDLINE
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