ArticlePloS one2013
Protein kinase CK2 inhibition down modulates the NF-κB and STAT3 survival pathways, enhances the cellular proteotoxic stress and synergistically boosts the cytotoxic effect of bortezomib on multiple myeloma and mantle cell lymphoma cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 91 citations in OpenAlex.
- A Phase 2 study of bortezomib combined with either idarubicin/cytarabine or cytarabine/etoposide in children with relapsed, refractory or secondary acute myeloid leukemia: a report from the Children's Oncology Group.Pediatric blood & cancer · 2014Trial
- CK2 in triple-negative breast cancer: oncogenic signaling networks and emerging CK2 inhibitor-based combination therapies.Clinical and experimental medicine · 2026Review
- Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.Clinical and experimental medicine · 2026Review
- Discovery of BMS-159, an Orally Active Imidazotriazine Pan-CK2 Inhibitor for the Treatment of Cancer.ACS medicinal chemistry letters · 2026Article
- The expression of MALAT1 long non-coding RNA is associated with good prognosis in mantle cell lymphoma.Scientific reports · 2026Article
- Discovery of new aurone derivatives as submicromolar CK2 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2025Article
- Pharmacological inhibition of casein kinase II attenuates metaflammation in a murine model of diet‑induced metabolic dysfunction.International journal of molecular medicine · 2025Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Single-cell transcriptomics identifies PDIA4 as a marker of progression and therapeutic vulnerability in multiple myeloma.Journal of translational medicine · 2025Article
- Decoding NF-κB: nucleocytoplasmic shuttling dynamics, synthetic modulation and post-therapeutic behavior in cancer.Molecular biology reports · 2025Review
- Article
- CK2 in the spotlight: decoding its role in hematological malignancies and therapeutic applications.Discover oncology · 2025Review
- Mechanism of antibacterial phytoconstituents: an updated review.Archives of microbiology · 2024Review
- Recent Advances in the Discovery of CK2 Inhibitors.ACS omega · 2024Review
- Protein kinase CK2α is overexpressed in classical hodgkin lymphoma, regulates key signaling pathways, PD-L1 and may represent a new target for therapy.Frontiers in immunology · 2024Article
- Beyond Bruton's tyrosine kinase inhibitors in mantle cell lymphoma: bispecific antibodies, antibody-drug conjugates, CAR T-cells, and novel agents.Journal of hematology & oncology · 2023Review
- Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Is It Still Possible to Think about HSP70 as a Therapeutic Target in Onco-Hematological Diseases?Biomolecules · 2023Review
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- Inhibition of casein kinase 2 sensitizes mantle cell lymphoma to venetoclax through MCL-1 downregulation.Haematologica · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CK2 is a pivotal pro-survival protein kinase in multiple myeloma that may likely impinge on bortezomib-regulated cellular pathways. In the present study, we investigated CK2 expression in multiple myeloma and mantle cell lymphoma, two bortezomib-responsive B cell tumors, as well as its involvement in bortezomib-induced cytotoxicity and signaling cascades potentially mediating bortezomib resistance. In both tumors, CK2 expression correlated with that of its activated targets NF-κB and STAT3 transcription factors. Bortezomib-induced proliferation arrest and apoptosis were significantly amplified by the simultaneous inhibition of CK2 with two inhibitors (CX-4945 and K27) in multiple myeloma and mantle cell lymphoma cell lines, in a model of multiple myeloma bone marrow microenvironment and in cells isolated from patients. CK2 inhibition empowered bortezomib-triggered mitochondrial-dependent cell death. Phosphorylation of NF-κB p65 on Ser529 (a CK2 target site) and rise of the levels of the endoplasmic reticulum stress kinase/endoribonuclease Ire1α were markedly reduced upon CK2 inhibition, as were STAT3 phospho Ser727 levels. On the contrary, CK2 inhibition increased phospho Ser51 eIF2α levels and enhanced the bortezomib-dependent accumulation of poly-ubiquitylated proteins and of the proteotoxic stress-associated chaperone Hsp70. Our data suggest that CK2 over expression in multiple myeloma and mantle cell lymphoma cells might sustain survival signaling cascades and can antagonize bortezomib-induced apoptosis at different levels. CK2 inhibitors could be useful in bortezomib-based combination therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.