CK2β Is a Gatekeeper of Focal Adhesions Regulating Cell Spreading

Abstract

CK2 is a hetero-tetrameric serine/threonine protein kinase made up of two CK2α/αʹ catalytic subunits and two CK2β regulatory subunits. The free CK2α 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 CK2β compared to CK2α 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 CK2β 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 CK2β 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 CK2β as a gatekeeper for cell spreading by restraining focal adhesion formation and invasion of mammary epithelial cells.

Characterization of RAGE and CK2 Expressions in Human Fetal Membranes

“…Beyond the mRNA expression results in this study, we did not observe any statistical changes in the CK2 subunit protein expression by Western blot analyses, the CK2 kinase activity, or the modification of their cellular localizations, which suggests a constant CK2 expression level in the FM layers throughout pregnancy. In addition to its role in controlling the substrate specificity and cellular localization of the CK2 holoenzyme complex, CK2β possesses important functions in inhibiting the induction of EMT during cancer progression [ 19 , 20 ] and as a gatekeeper of focal adhesions in cell spreading [ 38 ].…”