ArticleBlood2009
Bortezomib induces canonical nuclear factor-kappaB activation in multiple myeloma cells.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 194 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
194 citing papers in PubMed, 1 synthesis or guideline pooled it, 365 citations in OpenAlex.
- Signaling pathway mechanisms in pancreatic ductal adenocarcinoma tumor microenvironment and emerging targeting strategies for improved prognosis.Oncology reviews · 2026Pooled it
- Bortezomib is significantly beneficial for de novo pediatric AML patients with low phosphorylation of the NF-κB subunit RelA.Proteomics. Clinical applications · 2022Trial
- Clinical benefit of ixazomib plus lenalidomide-dexamethasone in myeloma patients with non-canonical NF-κB pathway activation.European journal of haematology · 2020Trial
- The novel orally active proteasome inhibitor K-7174 exerts anti-myeloma activity in vitro and in vivo by down-regulating the expression of class I histone deacetylases.The Journal of biological chemistry · 2013Trial
- Trial
- Bortezomib resistance in mantle cell lymphoma is associated with plasmacytic differentiation.Blood · 2011Trial
- Crosstalk Between mTOR and NF-κB Signaling Pathways in Clear Cell Renal Cell Carcinoma.International journal of molecular sciences · 2026Article
- Genetic architecture of multiple myeloma: From somatic alterations to germline susceptibility and clinical implications.Translational oncology · 2026Review
- Article
- Proteasome Targeting with Carfilzomib Induces Reactive Oxygen Species-Mediated Apoptosis in Hepatoblastoma.Cells · 2026Article
- STDrug enables spatially informed personalized drug repurposing from spatial transcriptomics.bioRxiv : the preprint server for biology · 2026Article
- Small molecule screening identifies cytotoxic endoplasmic reticulum-associated degradation inhibitors in multiple myeloma.Cell death & disease · 2026Article
- Phosphoproteomic Profiling of Multiple Myeloma Based on Ex Vivo Drug Sensitivity Resistance Testing Identifies Phosphorylation Signatures Associated with Drug Response.Biomolecules · 2026Article
- Kinetics of MM1.S Multiple Myeloma Cells in a 3D Polymer Particle Culture System with Bone Marrow Stromal Cells and Bortezomib.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Ambivalent Copper: Mechanistically Distinct Immune Effects Driving Innovation in Cancer Nanomedicine.Pharmaceutics · 2026Review
- Parasitic Infections and Carcinogenesis: Molecular Mechanisms, Immune Modulation, and Emerging Therapeutic Strategies.Oncology research · 2026Review
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- Decoding NF-κB: nucleocytoplasmic shuttling dynamics, synthetic modulation and post-therapeutic behavior in cancer.Molecular biology reports · 2025Review
- Augment proteasome inhibitor efficacy activates CD8Cell reports. Medicine · 2025Article
- An FDA-approved drug library screening identifies proteasome inhibitors as selective cytotoxic agents for angiosarcoma cells.British journal of cancer · 2025Review
134 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Bortezomib is a proteasome inhibitor with remarkable preclinical and clinical antitumor activity in multiple myeloma (MM) patients. The initial rationale for its use in MM was inhibition of nuclear factor (NF)-kappaB activity by blocking proteasomal degradation of inhibitor of kappaBalpha (IkappaBalpha). Bortezomib inhibits inducible NF-kappaB activity; however, its impact on constitutive NF-kappaB activity in MM cells has not yet been defined. In this study, we demonstrate that bortezomib significantly down-regulated IkappaBalpha expression and triggered NF-kappaB activation in MM cell lines and primary tumor cells from MM patients. Importantly, no inhibition of p65 (RelA) nuclear translocation was recognized after bortezomib treatment in a murine xenograft model bearing human MM cells. Bortezomib-induced NF-kappaB activation was mediated via the canonical pathway. Moreover, other classes of proteasome inhibitors also induced IkappaBalpha down-regulation associated with NF-kappaB activation. Molecular mechanisms whereby bortezomib induced IkappaBalpha down-regulation were further examined. Bortezomib triggered phosphorylation of IkappaB kinase (IKKbeta) and its upstream receptor-interacting protein 2, whereas IKKbeta inhibitor MLN120B blocked bortezomib-induced IkappaBalpha down-regulation and NF-kappaB activation, indicating receptor-interacting protein 2/IKKbeta signaling plays crucial role in bortezomib-induced NF-kappaB activation. Moreover, IKKbeta inhibitors enhanced bortezomib-induced cytotoxicity. Our studies therefore suggest that bortezomib-induced cytotoxicity cannot be fully attributed to inhibition of canonical NF-kappaB activity in MM cells.
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Registered trials
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.