CK2β Is a Gatekeeper of Focal Adhesions Regulating Cell Spreading

CK2 is a hetero-tetrameric serine/threonine protein kinase made up of two CK2 alpha/alpha' catalytic subunits and two CK2 beta regulatory subunits. The free CK2 alpha subunit and the tetrameric holoenzyme have distinct substrate specificity profiles, suggesting that the spatiotemporal organization of the individual CK2 subunits observed in living cells is crucial in the control of the many cellular processes that are governed by this pleiotropic kinase. Indeed, previous studies reported that the unbalanced expression of CK2 subunits is sufficient to drive epithelial to mesenchymal transition (EMT), a process involved in cancer invasion and metastasis. Moreover, sub-stoichiometric expression of CK2 beta compared to CK2 alpha in a subset of breast cancer tumors was correlated with the induction of EMT markers and increased epithelial cell plasticity in breast carcinoma progression. Phenotypic changes of epithelial cells are often associated with the activation of phosphotyrosine signaling. Herein, using phosphotyrosine enrichment coupled with affinity capture and proteomic analysis, we show that decreased expression of CK2 beta in MCF10A mammary epithelial cells triggers the phosphorylation of a number of proteins on tyrosine residues and promotes the striking activation of the FAK1-Src-PAX1 signaling pathway. Moreover, morphometric analyses also reveal that CK2 beta loss increases the number and the spatial distribution of focal adhesion signaling complexes that coordinate the adhesive and migratory processes. Together, our findings allow positioning CK2 beta as a gatekeeper for cell spreading by restraining focal adhesion formation and invasion of mammary epithelial cells.

Automated summary

CK2 is a hetero-tetrameric protein kinase with crucial roles in cellular processes and cancer progression. Lower expression of CK2 beta triggers phosphorylation of proteins and activates cell signaling pathways, impacting cell adhesion and migration processes.