Inhibition of protein kinase CK2 sensitizes non-small cell lung cancer cells to cisplatin via upregulation of PML

Yang, Bo; Yao, Jinhong; Bai, Li; Shao, Guoguang; Cui, Yongsheng

doi:10.1007/s11010-017-3081-2

Cited by 16 publications

(7 citation statements)

References 25 publications

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“…We have previously shown in prostate cancer that CK2 inhibition has a negative impact on mitochondrial health through decreased membrane potential and Ca 2+ flux [ 27 , 46 ]. CK2 has significant influence on numerous DNA repair and other pathways activated by radiation and cisplatin [ 27 , 47 , 48 , 49 ]; loss of CK2 improves sensitivity to cisplatin or radiation in numerous cancers, including head and neck cancer [ 42 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. CX-4945 blocks DNA repair after cisplatin or gemcitabine treatment [ 51 , 63 ], and next generation platinum Pt(IV) prodrugs conjugated with CX-4945 have shown efficacy in other cancer types [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines

Trembley

Kren

et al. 2021

Biomedicines

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Head and neck squamous cell carcinoma (HNSCC) can be categorized into human papillomavirus (HPV) positive or negative disease. Elevated protein kinase CK2 level and activity have been historically observed in HNSCC cells. Previous studies on CK2 in HNSCC did not generally include consideration of HPV(+) and HPV(-) status. Here, we investigated the response of HPV(+) and HPV(-) HNSCC cells to CK2 targeting using CX-4945 or siRNA downregulation combined with cisplatin treatment. HNSCC cell lines were examined for CK2 expression levels and activity and response to CX-4945, with and without cisplatin. CK2 levels and NFκB p65-related activity were high in HPV(+) HNSCC cells relative to HPV(-) HNSCC cells. Treatment with CX-4945 decreased viability and cisplatin IC50 in all cell lines. Targeting of CK2 increased tumor suppressor protein levels for p21 and PDCD4 in most instances. Further study is needed to understand the role of CK2 in HPV(+) and HPV(-) HNSCC and to determine how incorporation of the CK2-targeted inhibitor CX-4945 could improve cisplatin response in HNSCC.

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Section: Discussionmentioning

confidence: 99%

CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines

Trembley

Kren

et al. 2021

Biomedicines

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“…The nuclear scaffold protein promyelocytic leukemia gene (PML) has a dual role in cancer: it can act as the downstream target of oncogenic RAS and it can promote tumorigenesis (31). PML is a pro-apoptosis gene that can be indirectly suppressed by cisplatin-based systemic chemotherapy in nonsmall cell lung carcinoma (32). Additionally, it is suggested that it has a potential role in immune-modulatory approaches for treating lung cancer with aberrant PML degradation (33).…”

Section: Discussionmentioning

confidence: 99%

Identification of a Two-Gene (PML-EPB41) Signature With Independent Prognostic Value in Osteosarcoma

Liu

et al. 2020

Front. Oncol.

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Background: Osteosarcoma (OSA) is the most prevalent form of malignant bone cancer and it occurs predominantly in children and adolescents. OSA is associated with a poor prognosis and highest cause of cancer-related death. However, there are a few biomarkers that can serve as reasonable assessments of prognosis.Methods: Gene expression profiling data were downloaded from dataset GSE39058 and GSE21257 from the Gene Expression Omnibus database as well as TARGET database. Bioinformatic analysis with data integration was conducted to discover the significant biomarkers for predicting prognosis. Verification was conducted by qPCR and western blot to measure the expression of genes.Results: 733 seed genes were selected by combining the results of the expression profiling data with hub nodes in a human protein-protein interaction network with their gene functional enrichment categories identified. Following by Cox proportional risk regression modeling, a 2-gene (PML-EPB41) signature was developed for prognostic prediction of patients with OSA. Patients in the high-risk group had significantly poorer survival outcomes than in the low-risk group. Finally, the signature was validated and analyzed by the external dataset along with Kaplan-Meier survival analysis as well as biological experiment. A molecular gene model was built to serve as an innovative predictor of prognosis for patients with OSA.Conclusion: Our findings define novel biomarkers for OSA prognosis, which will possibly aid in the discovery of novel therapeutic targets with clinical applications.

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“…The rationale of targeting CK2 in combination with Cisplatin-based compounds is also supported by the observation of an increased CK2 expression in response to these drugs: this was reported by Yang et al [76], who observed down-regulation of the tumor suppressor PML in cisplatin-treated lung cancer cells, as a consequence of CK2α overexpression.…”

Section: Main Textmentioning

confidence: 81%

Role of protein kinase CK2 in antitumor drug resistance

Borgo

Ruzzene

2019

J Exp Clin Cancer Res

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Drug resistance represents the major reason of pharmacological treatment failure. It is supported by a broad spectrum of mechanisms, whose molecular bases have been frequently correlated to aberrant protein phosphorylation. CK2 is a constitutively active protein kinase which phosphorylates hundreds of substrates; it is expressed in all cells, but its level is commonly found higher in cancer cells, where it plays anti-apoptotic, pro-migration and pro-proliferation functions. Several evidences support a role for CK2 in processes directly responsible of drug resistance, such as drug efflux and DNA repair; moreover, CK2 intervenes in signaling pathways which are crucial to evade drug response (as PI3K/AKT/PTEN, NF-κB, β-catenin, hedgehog signaling, p53), and controls the activity of chaperone machineries fundamental in resistant cells. Interestingly, a panel of specific and effective inhibitors of CK2 is available, and several examples are known of their efficacy in resistant cells, with synergistic effect when used in combination with conventional drugs, also in vivo. Here we analyze and discuss evidences supporting the hypothesis that CK2 targeting represents a valuable strategy to overcome drug resistance.

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Inhibition of protein kinase CK2 sensitizes non-small cell lung cancer cells to cisplatin via upregulation of PML

Cited by 16 publications

References 25 publications

CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines

CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines

Identification of a Two-Gene (PML-EPB41) Signature With Independent Prognostic Value in Osteosarcoma

Role of protein kinase CK2 in antitumor drug resistance

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