Protein kinase CK2 in breast cancer: the CK2β regulatory subunit takes center stage in epithelial plasticity

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• 作者：Odile Filhol ; Sofia Giacosa ; Yann Wallez…
• 关键词：Protein kinase CK2 catalytic subunit (CK2α) ; Protein kinase CK2 regulatory subunit (CK2β) ; Substrate specificity ; Asymmetric subunit expression ; Glycogen synthase kinase 3 beta (GSK3β) ; Epithelial ; to ; mesenchymal transition (EMT) ; Zinc finger protein Snail1 ; Forkhead box protein C2 (Foxc2) ; Homeobox protein SIX1 ; Hallmarks of cancer
• 刊名：Cellular and Molecular Life Sciences (CMLS)
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：72
• 期：17
• 页码：3305-3322
• 全文大小：1,893 KB
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• 作者单位：Odile Filhol (1) (2) (3)
  Sofia Giacosa (1) (2) (3)
  Yann Wallez (1) (2) (3)
  Claude Cochet (1) (2) (3)
  
  1. Institut National de la Santé et de la Recherche Médicale, U1036, Grenoble, France
  2. Institute of Life Sciences Research and Technologies, Biology of Cancer and Infection, Commissariat à l’Energie Atomique, Grenoble, France
  3. Unité Mixte de Recherche-S1036, University of Grenoble Alpes, Grenoble, France
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Cell Biology
  Biomedicine
  Life Sciences
  Biochemistry
  
• 出版者：Birkh盲user Basel
• ISSN：1420-9071

文摘

Structurally, protein kinase CK2 consists of two catalytic subunits (α and α- and two regulatory subunits (β), which play a critical role in targeting specific CK2 substrates. Compelling evidence shows the complexity of the CK2 cellular signaling network and supports the view that this enzyme is a key component of regulatory protein kinase networks that are involved in several aspects of cancer. CK2 both activates and suppresses the expression of a number of essential oncogenes and tumor suppressors, and its expression and activity are upregulated in blood tumors and virtually all solid tumors. The prognostic significance of CK2α expression in association with various clinicopathological parameters highlighted this kinase as an adverse prognostic marker in breast cancer. In addition, several recent studies reported its implication in the regulation of the epithelial-to-mesenchymal transition (EMT), an early step in cancer invasion and metastasis. In this review, we briefly overview the contribution of CK2 to several aspects of cancer and discuss how in mammary epithelial cells, the expression of its CK2β regulatory subunit plays a critical role in maintaining an epithelial phenotype through CK2-mediated control of key EMT-related transcription factors. Importantly, decreased CK2β expression in breast tumors is correlated with inefficient phosphorylation and nuclear translocation of Snail1 and Foxc2, ultimately leading to EMT induction. This review highlights the pivotal role played by CK2β in the mammary epithelial phenotype and discusses how a modest alteration in its expression may be sufficient to induce dramatic effects facilitating the early steps in tumor cell dissemination through the coordinated regulation of two key transcription factors.