Nuclear localization of the CK2α-subunit correlates with poor prognosis in clear cell renal cell carcinoma

Rabjerg, Maj; Guerra, Bárbara; Oliván-Viguera, Aida; Mikkelsen, Minne Line Nedergaard; Köhler, Ralf; Issinger, O.-G.; Marcussen, Niels

doi:10.18632/oncotarget.13693

Cited by 24 publications

(32 citation statements)

References 50 publications

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“…find increased CK2 activity, and increase in CK2α, CK2α’ and CK2β protein levels in renal cell carcinoma in 15 patients [ 79 ]. Similarly, other renal clear cell carcinoma studies show increase in CK2 activity [ 36 , 80 ]. Timofeeva et al .…”

Section: Results and Discussion: Ck2 Transcript Expression Levels Andsupporting

confidence: 53%

“…This observation on decreased transcript levels is in conflict with our analysis and that of Rabjerg et al . [ 36 , 39 ]. Rabjerg et al .…”

Section: Results and Discussion: Ck2 Transcript Expression Levels Andmentioning

confidence: 99%

“…In addition, Rabjerg et al . find that high CK2α transcript expression and high nuclear CK2α staining correlate with poor overall survival, disease specific survival and progression free survival in patients with renal cell carcinoma [ 36 , 39 ]. In summary, CK2αP , and CK2α transcript and protein have a prognostic value in renal cell carcinoma; and nuclear CK2α protein, CK2α and CK2α ’ transcripts have a diagnosis value.…”

Section: Results and Discussion: Ck2 Transcript Expression Levels Andmentioning

confidence: 99%

“…Importantly, recent studies show that CK2 transcripts could have a diagnostic value (e.g. CK2α and CK2α’ in renal cell carcinoma [ 36 ] ; CK2β in invasive ductal and lobular breast carcinoma [ 9 ]). Furthermore, CK2 transcript levels could have a prognostic value in cancers (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Cancer-type dependent expression of CK2 transcripts

2017

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A multitude of proteins are aberrantly expressed in cancer cells, including the oncogenic serine-threonine kinase CK2. In a previous report, we found increases in CK2 transcript expression that could explain the increased CK2 protein levels found in tumors from lung and bronchus, prostate, breast, colon and rectum, ovarian and pancreatic cancers. We also found that, contrary to the current notions about CK2, some CK2 transcripts were downregulated in several cancers. Here, we investigate all other cancers using Oncomine to determine whether they also display significant CK2 transcript dysregulation. As anticipated from our previous analysis, we found cancers with all CK2 transcripts upregulated (e.g. cervical), and cancers where there was a combination of upregulation and/or downregulation of the CK2 transcripts (e.g. sarcoma). Unexpectedly, we found some cancers with significant downregulation of all CK2 transcripts (e.g. testicular cancer). We also found that, in some cases, CK2 transcript levels were already dysregulated in benign lesions (e.g. Barrett’s esophagus). We also found that CK2 transcript upregulation correlated with lower patient survival in most cases where data was significant. However, there were two cancer types, glioblastoma and renal cell carcinoma, where CK2 transcript upregulation correlated with higher survival. Overall, these data show that the expression levels of CK2 genes is highly variable in cancers and can lead to different patient outcomes.

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Section: Results and Discussion: Ck2 Transcript Expression Levels Andsupporting

confidence: 53%

“…This observation on decreased transcript levels is in conflict with our analysis and that of Rabjerg et al . [ 36 , 39 ]. Rabjerg et al .…”

Section: Results and Discussion: Ck2 Transcript Expression Levels Andmentioning

confidence: 99%

Section: Results and Discussion: Ck2 Transcript Expression Levels Andmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cancer-type dependent expression of CK2 transcripts

2017

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“…This is not the first time that CK2 could be viewed as a prognostic marker for cancer. Elevated levels of CK2α corresponded with a worse prognosis in glioblastoma [7], breast [18], ovarian [18], gastric cancer [19,20], renal clear cell carcinoma [21], AML [20,22], liver cancer [23,24], and sarcomas [20]. High expression of CK2β lead to a poor prognosis in lung adenocarcinoma [18], breast [18], gastric cancer [20,25], and head and neck cancer [20].…”

Section: Ck2 and Mb Clinical Relevancementioning

confidence: 99%

Casein kinase 2 inhibition sensitizes medulloblastoma to temozolomide

et al. 2019

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Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Since surviving patients experience severe neurocognitive disabilities, better and more effective treatments are needed to enhance their quality of life. Casein kinase 2 (CK2) is known to regulate cell growth and survival in multiple cancers; however, the role of CK2 in MB is currently being studied. In this study, we verified the importance of CK2 in MB tumorigenesis and discovered that inhibition of CK2 using the small molecule inhibitor, CX-4945, can sensitize MB cells to a well-known and tolerated chemotherapeutic, temozolomide (TMZ). To study the role of CK2 in MB we modulated CK2 expression in multiple MB cells. Exogenous expression of CK2 enhanced cell growth and tumor growth in mice, while depletion or inhibition of CK2 expression decreased MB tumorigenesis. Treatment with CX-4945 reduced MB growth and increased apoptosis. We conducted a highthroughput screen where 4000 small molecule compounds were analyzed to identify compounds that increased the antitumorigenic properties of CX-4945. TMZ was found to work synergistically with CX-4945 to decrease cell survival and increase apoptosis in MB cells. O-6-methylguanine-DNA methyltransferase (MGMT) activity is directly correlated to TMZ sensitivity. We found that loss of CK2 activity reduced β-catenin expression, a known MGMT regulator, which in turn led to a decrease in MGMT expression and an increased sensitivity to TMZ. Our findings show that CK2 is important for MB maintenance and that treatment with CX-4945 can sensitize MB cells to TMZ treatment.

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Benzothiazole derivatives in the design of antitumor agents

Paoletti,

Supuran

2024

Archiv der Pharmazie

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Benzothiazoles are a class of heterocycles with multiple applications as anticancer, antibiotic, antiviral, and anti‐inflammatory agents. Benzothiazole is a privileged scaffold in drug discovery programs for modulating a variety of biological functions. This review focuses on the design and synthesis of new benzothiazole derivatives targeting hypoxic tumors. Cancer is a major health problem, being among the leading causes of death. Tumor‐hypoxic areas promote proliferation, malignancy, and resistance to drug treatment, leading to the dysregulation of key signaling pathways that involve drug targets such as vascular endothelial growth factor, epidermal growth factor receptor, hepatocyte growth factor receptor, dual‐specificity protein kinase, cyclin‐dependent protein kinases, casein kinase 2, Rho‐related coil formation protein kinase, tunica interna endothelial cell kinase, cyclooxygenase‐2, adenosine kinase, lysophosphatidic acid acyltransferases, stearoyl‐CoA desaturase, peroxisome proliferator‐activated receptors, thioredoxin, heat shock proteins, and carbonic anhydrase IX/XII. In turn, they regulate angiogenesis, proliferation, differentiation, and cell survival, controlling the cell cycle, inflammation, the immune system, and metabolic alterations. A wide diversity of benzothiazoles were reported over the last years to interfere with various proteins involved in tumorigenesis and, more specifically, in hypoxic tumors. Many hypoxic targets are overexpressed as a result of the hypoxia‐inducible factor activation cascade and may not be present in normal tissues, providing a potential strategy for selectively targeting hypoxic cancers.

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Nuclear localization of the CK2α-subunit correlates with poor prognosis in clear cell renal cell carcinoma

Cited by 24 publications

References 50 publications

Cancer-type dependent expression of CK2 transcripts

Cancer-type dependent expression of CK2 transcripts

Casein kinase 2 inhibition sensitizes medulloblastoma to temozolomide

Benzothiazole derivatives in the design of antitumor agents

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