title: Suppression of casein kinase 2 sensitizes tumor cells to antitumor TRAIL therapy by regulating the phosphorylation and localization of p65 in prostate cancer.
abstract: In the United States, prostate cancer (PCa) is the most commonly diagnosed cancer in males. For PCa at the late hormone-refractory stage, substantial improvement in treatment strategies is critically needed. TNF-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent, but both intrinsic and acquired resistance to TRAIL poses a huge problem in establishing clinically effective TRAIL therapies. In the present study, we examined the role played by casein kinase 2 (CK2) in the TRAIL‑induced nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB) pathway in a PCa cell line. Downregulation of CK2 combined with a sub-dose of TRAIL suppressed p65 phosphorylation at serine 536. The combination treatment of TRAIL and the CK2 inhibitor decreased p65 nuclear translocation. Under the treatment of a sub-dose of TRAIL, downregulation of CK2, using both genetic and pharmacological approaches, decreased the transcriptional activity of NF-κB and the expression of NF-κB downstream anti-apoptosis genes. Therefore, we provided novel molecular mechanistic insight reporting that CK2 regulates the sensitivity of PCa cells to the antitumor effect of TRAIL. This is important for understanding how the TRAIL pathway is disrupted in PCa and may help to develop an effective combinatorial therapy for PCa.
authors.affiliation: Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Gang
authors.affiliation: Department of Orthopedics, The Second Hospital of Jilin University, Changchun, Jilin 130042, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Urology, Jilin Oncological Hospital, Changchun, Jilin 130021, P.R. China.
authors.forename: Yingdi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
authors.forename: Liya
authors.initials: L
authors.lastname: Ding
authors.affiliation: Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000627:therapeutic use*; D019892:eIF-2 Kinase / Q000235:genetics* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016328:NF-kappa B; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D047390:Casein Kinase II; D019892:eIF-2 Kinase