Targeting protein kinase CK2 suppresses bladder cancer cell survival via the glucose metabolic pathway.

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.

• Authors: Xiaolei Zhang, Xiao Yang, Chengdi Yang, Peng Li, Wenbo Yuan, Xiaheng Deng, Yidong Cheng, Pengchao Li, Haiwei Yang, Jun Tao, Qiang Lu
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 52 Pg. 87361-87372 (Dec 27 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27888634 (Publication Type: Journal Article)

Chemical References

• Naphthyridines
• Phenazines
• silmitasertib
• CSNK2A1 protein, human
• Casein Kinase II
• Glucose

Topics

• Adult
• Aged
• Animals
• Casein Kinase II (analysis, antagonists & inhibitors)
• Cell Line, Tumor
• Cell Survival
• Female
• Glucose (metabolism)
• Humans
• Immunohistochemistry
• Male
• Metabolic Networks and Pathways
• Mice
• Mice, Inbred BALB C
• Middle Aged
• Naphthyridines (therapeutic use)
• Phenazines
• Urinary Bladder Neoplasms (drug therapy, metabolism, pathology)