Augmented expression of
protein kinase CK2 is associated with hyperproliferation and resistance to apoptosis in
cancer cells. Effects of CK2 are at least partially linked to signaling via the Wnt/β-
catenin pathway, which is dramatically enhanced in
colon cancer.
Cyclooxygenase-2 (COX-2), a Wnt/β-
catenin target gene, has been associated with enhanced
cancer progression and
metastasis. However, the possibility that a connection may exist between CK2 and COX-2 has not been explored previously. Here we investigated changes in COX-2 expression and activity upon CK2 modulation and evaluated how these changes affected cell viability. COX-2 expression and cell viability decreased upon selective inhibition of COX-2 with
SC-791 or CK2 with
2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT), both in human colon (HT29-ATCC, HT29-US, DLD-1) and breast (ZR-75)
cancer cells, as well as in human embryonic kidney (HEK-293T) cells. On the other hand, ectopic CK2α expression promoted up-regulation of COX-2 by activating the Wnt/β-
catenin pathway in HEK-293T cells. Noteworthy, over-expression of either CK2α, β-
catenin or COX-2, as well as supplementation of the medium with
prostaglandin E2 (
PGE2), all were individually sufficient to overcome limitations in cell viability triggered by CK2 inhibition either upon addition of DMAT or over-expression of a dominant negative CK2α variant. Altogether, these findings provide new insight to the role of CK2 in
cancer by up-regulating COX-2 expression and thereby
PGE2 production.