1460

CSNK2B

Protein kinase CK2 participates in the regulation of fundamental cellular processes. Among these processes, cell polarity and cell morphology are controlled by this enzyme probably through the phosphorylation of key proteins. To further study the involvement of CK2 in these processes, we showed that in epithelial cells, the regulatory CK2beta subunit was required for LKB1-dependent polarization and cell adhesion. Moreover, CK2beta silencing in MCF10A mammary epithelial cells triggered changes in their morphology correlated with the acquisition of mesenchymal phenotype, which were reminiscent to TGFbeta-induced epithelial-to-mesenchymal-transition (EMT). TGFbeta has emerged as a major inducer of EMT both in vitro and in vivo. We found that among the TGFbeta isoforms, TGFbeta2 expression was strongly induced in CK2beta-knockdown cells. However, the EMT phenotype induced in response to CK2beta silencing was not abolished by blocking the TGFbeta signaling pathway at TGFbeta receptor level, suggesting that alternative pathways might be involved. Given the importance of CK2 in tumorigenesis, a dysregulation of CK2beta expression might contribute to EMT induction during cancer progression.

TGFbeta1/Smad, Wnt/beta-catenin and snail1 are preferentially activated in renal tubular epithelia after injury, leading to epithelial-mesenchymal transition (EMT). The stress response is coupled to EMT and kidney injury; however, the underlying mechanism of the stress response in EMT remains elusive. AMP-activated protein kinase (AMPK) signalling is responsive to stress and regulates cell energy balance and differentiation. We found that knockdown of AMPKalpha, especially AMPKalpha2, enhanced EMT by up-regulating beta-catenin and Smad3 in vitro. AMPKalpha2 deficiency enhanced EMT and fibrosis in a murine unilateral ureteral obstruction (UUO) model. AMPKalpha2 deficiency also increased the expression of chemokines KC and MCP-1, along with enhanced infiltration of inflammatory cells into the kidney after UUO. CK2beta interacted physically with AMPKalpha and enhanced AMPKalpha Thr172 phosphorylation and its catalytic activity. Thus, activated AMPKalpha signalling suppresses EMT and secretion of chemokines in renal tubular epithelia through interaction with CK2beta to attenuate renal injury.CI - Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.