ArticleOncotarget2014
Bortezomib induces AMPK-dependent autophagosome formation uncoupled from apoptosis in drug resistant cells.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.International journal of molecular sciences · 2023Pooled it
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- Decoding NF-κB: nucleocytoplasmic shuttling dynamics, synthetic modulation and post-therapeutic behavior in cancer.Molecular biology reports · 2025Review
- NCX1/CaCell communication and signaling : CCS · 2024Article
- Autophagy and oxidative stress modulation mediate Bortezomib resistance in prostate cancer.PloS one · 2024Article
- Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma.International journal of molecular sciences · 2023Review
- An Integrated Methodology to Quantify the Glycolytic Stress in Plasma Cell Myeloma in Response to Cytotoxic Drugs.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Autophagy-related mechanisms for treatment of multiple myeloma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Autophagy in Hematological Malignancies.Cancers · 2022Review
- Therapeutic implications of mitochondrial stress-induced proteasome inhibitor resistance in multiple myeloma.Science advances · 2022Article
- Review
- Adaptive response of resistant cancer cells to chemotherapy.Cancer biology & medicine · 2020Review
- AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury.Nature metabolism · 2020Article
- Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple Myeloma.Translational oncology · 2018Review
- Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells.Cancer research · 2017Article
- DDX53 Promotes Cancer Stem Cell-Like Properties and Autophagy.Molecules and cells · 2017Article
- Bortezomib-resistance is associated with increased levels of proteasome subunits and apoptosis-avoidance.Oncotarget · 2016Article
- High throughput chemical library screening identifies a novel p110-δ inhibitor that potentiates the anti-myeloma effect of bortezomib.Oncotarget · 2016Article
- Induction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib.Oncotarget · 2016Article
- Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The proteasome inhibitor bortezomib is an effective anti-cancer agent for the plasma cell malignancy multiple myeloma but clinical response is hindered by the emergence of drug resistance through unknown mechanisms. Drug sensitive myeloma cells were exposed to bortezomib to generate drug resistant cells that displayed a significant increase in subunits of the energy sensor AMP-activated protein kinase (AMPK). AMPK activity in resistant cells was increased and bortezomib resistant cells contained a ~4-fold greater level of autophagosomes than drug sensitive cells. Real-time measurements indicated that bortezomib reduced the oxygen consumption rate in drug sensitive cells more readily than in resistant cells. Genetic ablation of AMPK activity reduced the bortezomib effect on autophagy. The autophagy-related gene (Atg)5 is required for autophagosome formation and enhances cellular susceptibility to apoptotic stimuli. Atg5 knockout eliminated bortezomib-induced autophagosome formation and reduced susceptibility to bortezomib. Bortezomib treatment of myeloma cells lead to ATG5 cleavage through a calpain-dependent manner while calpain inhibition or a calpain-insensitive Atg5 mutant promoted bortezomib-resistance. In contrast, AICAR, an AMPK activator, enhanced bortezomib-induced cleavage of ATG5 and increased bortezomib-induced killing. Taken together, the results demonstrate that ATG5 cleavage provokes apoptosis and represents a molecular link between autophagy and apoptosis with therapeutic implications.
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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.