ArticleMolecular oncology2020
NEK2 induces autophagy-mediated bortezomib resistance by stabilizing Beclin-1 in multiple myeloma.
Article in Molecular oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 118 citations in OpenAlex.
- NEK2 promotes trastuzumab resistance in gastric cancer through WTAP/YTHDF1-dependent m6A regulation of FN1.Molecular biology reports · 2026Article
- Article
- An oncolytic vaccinia virus encoding CD47 nanobody potentiates antitumor immunity in multiple myeloma.iScience · 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
- MIR4726Cell communication and signaling : CCS · 2025Article
- Role of the USP family in autophagy regulation and cancer progression.Apoptosis : an international journal on programmed cell death · 2025Review
- The Transcription Axes ERK-Elk1, JNK-cJun, and JAK-STAT Promote Autophagy Activation and Proteasome Inhibitor Resistance in Prostate Cancer Cells.Current issues in molecular biology · 2025Article
- ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review).Oncology letters · 2025Review
- NEK2 Control of Esophageal Squamous Cell Carcinoma Growth Based on Circadian Oscillation.Cancer science · 2025Article
- A novel indirubin- 3-monoxime derivative I3MV- 8b exhibits remarkable cytotoxicity against multiple myeloma by targeting TRIM28.Biomarker research · 2025Article
- Prognostic Value of PSMB5 and Correlations with LC3II and Reactive Oxygen Species Levels in the Bone Marrow Mononuclear Cells of Bortezomib-Resistant Multiple Myeloma Patients.Current issues in molecular biology · 2025Article
- Natural Compounds and their Nano-formulations in Combating Autophagy-mediated Drug Resistance in Human Cancers.Current topics in medicinal chemistry · 2025Review
- Nanoparticles Based Therapeutic Approaches in Oncogenic Viral Infections: A Review.International journal of nanomedicine · 2025Review
- NEK2 affects the ferroptosis sensitivity of gastric cancer cells by regulating the expression of HMOX1 through Keap1/Nrf2.Molecular and cellular biochemistry · 2025Article
- Role of NEK2 in tumorigenesis and tumor progression.Trends in molecular medicine · 2025Review
- Structural insights into Beclin 1 interactions with it's regulators for autophagy modulation.Computational and structural biotechnology journal · 2025Review
- Acquired Bortezomib Resistance in Multiple Myeloma: From Mechanisms to Strategy.Current treatment options in oncology · 2024Review
- Bortezomib elevates intracellular free FeAnnals of hematology · 2024Article
- Different Strategies to Overcome Resistance to Proteasome Inhibitors-A Summary 20 Years after Their Introduction.International journal of molecular sciences · 2024Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 4 countries.
Funding
Abstract
NEK2 is associated with drug resistance in multiple cancers. Our previous studies indicated that high NEK2 confers inferior survival in multiple myeloma (MM); thus, a better understanding of the mechanisms by which NEK2 induces drug resistance in MM is required. In this study, we discovered that NEK2 enhances MM cell autophagy, and a combination of autophagy inhibitor chloroquine (CQ) and chemotherapeutic bortezomib (BTZ) significantly prevents NEK2-induced drug resistance in MM cells. Interestingly, NEK2 was found to bind and stabilize Beclin-1 protein but did not affect its mRNA expression and phosphorylation. Moreover, autophagy enhanced by NEK2 was significantly prevented by knockdown of Beclin-1 in MM cells, suggesting that Beclin-1 mediates NEK2-induced autophagy. Further studies demonstrated that Beclin-1 ubiquitination is decreased through NEK2 interaction with USP7. Importantly, knockdown of Beclin-1 sensitized NEK2-overexpressing MM cells to BTZ in vitro and in vivo. In conclusion, we identify a novel mechanism whereby autophagy is activated by the complex of NEK2/USP7/Beclin-1 in MM cells. Targeting the autophagy signaling pathway may provide a promising therapeutic strategy to overcome NEK2-induced drug resistance in MM.
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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.