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Protein Kinase CK2 and cellular plasticity

Researchers at our laboratory show that mesenchymal cells whose CK2 protein kinase ß subunit expression has been attenuated have cancerous stem cell properties.

Published on 5 December 2017
Cellular plasticity allows cells to adapt to their environment. Thus, epithelial cells acquire migratory properties when they have to move. This reversible phenomenon, called the epithelio-mesenchymal transition, or EMT, is physiological process also used by cancer cells to leave the primary tumor to form metastases. This widely studied mechanism could be induced by specific extra-or-intra cellular factors including hypoxia. While the EMT has long been associated with the acquisition of mobility and invasiveness, the association between this programme and the entrance into a stem cell-like state has been documented. Precisely how EMT programmes facilitate the entrance of those cells into stem cell states remains elusive.

Researchers from the laboratory have previously shown that one way to induce EMT in mammary epithelial cells was to decrease the expression level of the regulatory subunits of the protein kinase CK2 [Reference]. This ubiquitous enzyme is composed of two α catalytic subunits and two β regulatory subunits (Figure). The imbalance between these subunits in favor of CK2α modulates the phosphorylation of specific proteins including EMT-activating transcription factors, thereby inducing EMT [Reference].

The researchers further characterized the cells in which they had attenuated the expression of CK2β (ΔCK2β cells) showing that they have lost their polarity and are no longer able to form acini like parental cells (Figure). They also grow in the absence of anchorage and are resistant to Paclitaxel, an anti-cancer drug. Studying more precisely their capacity to behave as stem cells ("stemness"), they found that the mRNA and microRNA profiles of these cells are very similar to the profiles observed in the case of mesenchymal cells. This analysis also showed that CK2β-depleted cells have several activated genes in common with stem cells and even suggest that they possess properties, linking them to the concept of cancer stem cells. 

These results demonstrate the important role of the β subunit of CK2 in the control of cellular plasticity encouraging to identify CK2 protein substrate whose phosphorylation is modulated by the presence or absence of this CK2 regulatory subunit. Thus, this may help to identify new markers in tumors that provide cells with the ability to migrate and form metastases, a major issue in oncology.

Diagram representing an epithelial cell where CK2 is composed of 2 types of subunits, and a mesenchymal cell where CK2β is absent. Images A and B are those of cells grown in an extracellular matrix (Matrigel type) with a marking of the nuclei (blue), the outlines of the cells (green) and the Golgi (red). Epithelial cells grow as acini (A) whereas ΔCK2β cells are unable to form (B), just like cancer stem cells.

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