ArticleThe Journal of clinical investigation2018
Destabilizing NEK2 overcomes resistance to proteasome inhibition in multiple myeloma.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 91 citations in OpenAlex.
- NEK2 promotes trastuzumab resistance in gastric cancer through WTAP/YTHDF1-dependent m6A regulation of FN1.Molecular biology reports · 2026Article
- Dexamethasone activates anti-tumor immunity in multiple myeloma by dismantling the GR-PPP1CB complex to restore STING/IRF3 signaling.Journal for immunotherapy of cancer · 2026Article
- Human oncogenic herpesvirus latency proteins activate NEK2 to promote chromosomal instability and tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- USP7 promotes follicular thyroid carcinoma progression and sorafenib resistance by activating NEK2/ATG5-mediated autophagy.Histology and histopathology · 2026Article
- USP7 at the Crossroads of Ubiquitin Signaling, Cell Cycle, and Tumorigenesis.Molecules (Basel, Switzerland) · 2025Review
- NEK Family Kinases: Structure, Function, and Role in Disease.Biomolecules · 2025Review
- InhibitingBiomedicines · 2025Article
- NEK2 regulates B cell function and the severity of experimental autoimmune encephalomyelitis.Journal of neuroinflammation · 2025Article
- A prognostic model for multiple myeloma based on lipid metabolism related genes.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- NEK6 functions as an oncogene to promote the proliferation and metastasis of ovarian cancer.Journal of Cancer · 2025Article
- Role of NEK2 in tumorigenesis and tumor progression.Trends in molecular medicine · 2025Review
- NEK2 affects the ferroptosis sensitivity of gastric cancer cells by regulating the expression of HMOX1 through Keap1/Nrf2.Molecular and cellular biochemistry · 2025Article
- Disrupting USP39 deubiquitinase function impairs the survival and migration of multiple myeloma cells through ZEB1 degradation.Journal of experimental & clinical cancer research : CR · 2024Article
- LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma.Haematologica · 2024Article
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Cheminformatics-aided discovery of potential allosteric site modulators of ubiquitin-specific protease 7.Scientific reports · 2024Article
- Single-cell sequencing analysis of multiple myeloma heterogeneity and identification of new theranostic targets.Cell death & disease · 2024Article
- Troponin T1 in tumorigenesis and immune modulation: Insights into multiple cancers and kidney renal clear cell carcinoma.Journal of cellular and molecular medicine · 2024Article
- Drug resistance mechanisms and treatment strategies mediated by Ubiquitin-Specific Proteases (USPs) in cancers: new directions and therapeutic options.Molecular cancer · 2024Review
- HSPA12A maintains aerobic glycolytic homeostasis and Histone3 lactylation in cardiomyocytes to attenuate myocardial ischemia/reperfusion injury.JCI insight · 2024Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Drug resistance remains the key problem in cancer treatment. It is now accepted that each myeloma patient harbors multiple subclones and subclone dominance may change over time. The coexistence of multiple subclones with high or low chromosomal instability (CIN) signature causes heterogeneity and drug resistance with consequent disease relapse. In this study, using a tandem affinity purification-mass spectrometry (TAP-MS) technique, we found that NEK2, a CIN gene, was bound to the deubiquitinase USP7. Binding to USP7 prevented NEK2 ubiquitination resulting in NEK2 stabilization. Increased NEK2 kinase levels activated the canonical NF-κB signaling pathway through the PP1α/AKT axis. Newly diagnosed myeloma patients with activated NF-κB signaling through increased NEK2 activity had poorer event-free and overall survivals based on multiple independent clinical cohorts. We also found that NEK2 activated heparanase, a secreted enzyme, responsible for bone destruction in an NF-κB-dependent manner. Intriguingly, both NEK2 and USP7 inhibitors showed great efficacy in inhibiting myeloma cell growth and overcoming NEK2-induced and -acquired drug resistance in xenograft myeloma mouse models.
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