CK2 inhibition induced PDK4-AMPK axis regulates metabolic adaptation and survival responses in glioma.
Understanding mechanisms that link aberrant metabolic adaptation and pro-survival responses in glioma cells is crucial towards the development of new anti-glioma therapies. As we have previously reported that CK2 is associated with glioma cell survival, we evaluated its involvement in the regulation of glucose metabolism. Inhibition of CK2 increased the expression of metabolic regulators, PDK4 and AMPK along with the key cellular energy sensor CREB. This increase was concomitant with altered metabolic profile as characterized by decreased glucose uptake in a PDK4 and AMPK dependent manner. Increased PDK4 expression was CREB dependent, as exogenous inhibition of CREB functions abrogated CK2 inhibitor mediated increase in PDK4 expression. Interestingly, PDK4 regulated AMPK phosphorylation which in turn affected cell viability in CK2 inhibitor treated glioma cells. CK2 inhibitor 4,5,6,7-Tetrabromobenzotriazole (TBB) significantly retarded the growth of glioma xenografts in athymic nude mouse model. Coherent with the in vitro findings, elevated senescence, pAMPK and PDK4 levels were also observed in TBB-treated xenograft tissue. Taken together, CK2 inhibition in glioma cells drives the PDK4-AMPK axis to affect metabolic profile that has a strong bearing on their survival.
['Dixit|Deobrat|D|', 'Ahmad|Fahim|F|', 'Ghildiyal|Ruchi|R|', 'Joshi|Shanker Datt|SD|', 'Sen|Ellora|E|']
D055372:AMP-Activated Protein Kinases D000255:Adenosine Triphosphate D000818:Animals D001932:Brain Neoplasms D047390:Casein Kinase II D045744:Cell Line, Tumor D049109:Cell Proliferation D002470:Cell Survival D016922:Cellular Senescence D017362:Cyclic AMP Response Element-Binding Protein D005910:Glioma D005947:Glucose D006801:Humans D008819:Mice, Nude D010641:Phenotype D010766:Phosphorylation D017346:Protein Serine-Threonine Kinases D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase D012333:RNA, Messenger D015398:Signal Transduction D056564:Sirtuin 1 D014230:Triazoles D016159:Tumor Suppressor Protein p53 D023041:Xenograft Model Antitumor Assays
CK2 PDK4 AMPK CREB Glioblastoma