Abstract
Casein kinase 2 (CK2) is a constitutively active serine/threonine kinase that promotes cell proliferation and resists apoptosis. Elevated CK2 expression has been demonstrated in several solid tumors. The expression of CK2α in bladder cancer was elevated in tumor tissues compared with that in adjacent normal tissues. Amplified expression of CK2α was highly correlated with histological grade in bladder cancer(P = 0.024). Knockdown of CK2α in bladder cancer cell lines resulted in a reduction in tumor aerobic glycolysis, accompanied with lower phosphorylated AKT. Moreover, low CK2α levels suppressed cell growth, and similar results could be reproduced after treatment with CX-4945 with a dose-dependent response. CX-4945 inhibited migration and induced apoptosis. Furthermore, knockdown of CK2α decreased the tumorigenicity of bladder cancer cells in vivo. This study is the first to report that CK2 increases glucose metabolism in human bladder cancer. Blocking CK2 function may provide novel diagnostic and potential therapeutic.
Highlights
Bladder cancer was the sixth most commonly diagnosed cancer in males in 2012 worldwide and the most common malignancy of the urogenital tract
Consistent with the PCR results, CK2α protein expression was significantly higher in the BCa tissues compared with that in the adjacent tissues (Figure 1C). qRT-PCR analysis demonstrated that mRNA level of CK2α in six bladder cancer cell lines (T24, J82, EJ, 253J, TCC, and RT4) was increased compared with that in the normal urinary epithelial cell line sv-Huc (Figure 1D)
CK2α expression was positively associated with bladder cancer progression, suggesting that it played an oncogenic role in bladder cancer
Summary
Bladder cancer was the sixth most commonly diagnosed cancer in males in 2012 worldwide and the most common malignancy of the urogenital tract. Elevated level of CK2α has been observed in numerous cancers, including breast [10], prostate [11], lung [12, 13], head and neck [14], colorectal [15], gastric [16], and kidney [17]. These evidences validated that CK2 could be a potential cancer therapeutic target. CX4945 inhibits the activity of CK2α and CK2α’, resulted to suppression of activation of pro-survival signaling pathways and promotion of apoptosis in human glioblastoma, breast, prostate, and lung cancers [13, 18,19,20]
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