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Dysregulated Expression of Protein Kinase CK2 in Renal Cancer

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Protein Kinase CK2 Cellular Function in Normal and Disease States

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 12))

Abstract

Renal cell carcinomas (RCCs) have notoriously been shown to be refractory to traditional therapies including radiation and cytokine therapies. The use of molecularly targeted therapies against mTOR, VEGF, and other angiogenic factors has significantly improved the standards of care of this disease. Yet, improvements are still required as many of the current therapies are limited by acquired resistance. However, the recent development of molecular targeted therapies involving kinase inhibitors has changed the clinical management of RCCs. Protein kinase CK2 is critical for the activation of multiple pro-survival signaling pathways, and its catalytic activity is invariably elevated in various types of tumors. However, the precise role of CK2 has never been addressed in RCCs. In this study, we have analyzed the activity of CK2 and the expression of its subunits in a small cohort of RCC tumors. This analysis revealed, in the majority of tumor samples, an upregulation of the CK2 catalytic subunits that was not correlated with mRNA abundance in the majority of tumor samples. Moreover, relative levels of the three CK2 subunits varied significantly between tumor samples, and a positive correlation was observed between low CK2β expression and an upregulation of the ZEB2 mesenchymal marker in a subset of tumor samples. Using the CK2 inhibitor CX-4945 to downregulate the CK2 catalytic activity in 786-O cells as a model of VHL-deficient renal cancer cell line, we showed that CK2 represents a potential promising therapeutic target in RCCs.

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Acknowledgments

This research was supported by the INSERM, CEA, Ligue Nationale contre le Cancer (équipe labellisée 2010–2012), UJF, Ligue Régionale contre le Cancer (Isère), Fondation de France, ARC, and Projet CIBLE. We thank Marlène Debiossat for technical assistance.

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Authors and Affiliations

  1. INSERM, Unité 1036, Biology of Cancer and Infection, Grenoble, 38054, France

    Caroline Roelants, Sofia Giacosa, Eve Duchemin-Pelletier, Céline Tisseyre, Laure Schoutteten, Benoit Bestgen, Claude Cochet & Odile Filhol

  2. UJF-Grenoble 1, Biology of Cancer and Infection, Grenoble, 38041, France

    Caroline Roelants, Sofia Giacosa, Eve Duchemin-Pelletier, Céline Tisseyre, Laure Schoutteten, Benoit Bestgen, Claude Cochet & Odile Filhol

  3. CEA, DSV/iRTSV, Biology of Cancer and Infection, Grenoble, 38054, France

    Caroline Roelants, Sofia Giacosa, Eve Duchemin-Pelletier, Céline Tisseyre, Laure Schoutteten, Benoit Bestgen, Claude Cochet & Odile Filhol

  4. INSERM U 823, Institut A Bonniot, Université J Fourier, Grenoble, France

    Anne McLeer-Florin

  5. Département d’Anatomie et Cytologie Pathologiques et Plateforme de Génétique Moléculaire des Tumeurs, Pôle de Biologie et Pathologie, CHU Grenoble, Avenue Maquis du Grésivaudan, 38700, La Tronche, France

    Anne McLeer-Florin, Cédric Aubert, Pierre Champelovier, Jean Boutonnat, Dominique Pasquier, Maysoun Kassem & Laurence David-Boudet

  6. CEA, DSV/iRTSV, Biologie à Grande Echelle, Grenoble, 38054, France

    Catherine Pillet

  7. Centre hospitalo-universitaire Albert Michallon, service d’urologie, Grenoble, France

    Jean Luc Descotes, Jean-Jacques Rambeaud, Valentin Arnoux & Jean-Alexandre Long

  8. Centre hospitalo-universitaire Albert Michallon, service d’oncologie médicale, Grenoble, France

    Mathieu Laramas

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  1. Caroline Roelants
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Corresponding author

Correspondence to Odile Filhol .

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Editors and Affiliations

  1. Department of Laboratory Medicine and Pathology, University of Minnesota Medical School and Minneapolis VA Health Care System, Minneapolis, Minnesota, USA

    Khalil Ahmed

  2. Dept of Biochemistry & Molecular Biology, University of Southern Denmark, Odense, Denmark

    Olaf-Georg Issinger

  3. Department of Molecular Biology, The John Paul II Catholic U. of Lublin Institute of Biotechnology, Lublin, Poland

    Ryszard Szyszka

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Roelants, C. et al. (2015). Dysregulated Expression of Protein Kinase CK2 in Renal Cancer. In: Ahmed, K., Issinger, OG., Szyszka, R. (eds) Protein Kinase CK2 Cellular Function in Normal and Disease States. Advances in Biochemistry in Health and Disease, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-14544-0_14

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