ArticleOncotarget2015
Synergistic inhibition of autophagy and neddylation pathways as a novel therapeutic approach for targeting liver cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Inhibiting neddylation: A new strategy for tumor therapy.Journal of pharmaceutical analysis · 2025Review
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- KLHL3-dependent WNK4 degradation affected by potassium through the neddylation and autophagy pathway.BMC nephrology · 2023Article
- Major roles of the circadian clock in cancer.Cancer biology & medicine · 2023Review
- The Cellular and Developmental Roles of Cullins, Neddylation, and the COP9 Signalosome inFrontiers in physiology · 2022Review
- Role of autophagy in tumor response to radiation: Implications for improving radiotherapy.Frontiers in oncology · 2022Review
- UBE2M Drives Hepatocellular Cancer Progression as a p53 Negative Regulator by Binding to MDM2 and Ribosomal Protein L11.Cancers · 2021Article
- Neddylation regulation of mitochondrial structure and functions.Cell & bioscience · 2021Review
- Decreased KLHL3 expression is involved in the activation of WNK-OSR1/SPAK-NCC cascade in type 1 diabetic mice.Pflugers Archiv : European journal of physiology · 2021Article
- Inhibition of deubiquitination by PR-619 induces apoptosis and autophagy via ubi-protein aggregation-activated ER stress in oesophageal squamous cell carcinoma.Cell proliferation · 2021Article
- Neddylation inhibition activates the protective autophagy through NF-κB-catalase-ATF3 Axis in human esophageal cancer cells.Cell communication and signaling : CCS · 2020Article
- An overactive neddylation pathway serves as a therapeutic target and MLN4924 enhances the anticancer activity of cisplatin in pancreatic cancer.Oncology letters · 2019Article
- Rosemary (Rosmarinus officinalis) extract causes ROS-induced necrotic cell death and inhibits tumor growth in vivo.Scientific reports · 2019Article
- Protein neddylation and its alterations in human cancers for targeted therapy.Cellular signalling · 2018Review
- Chloroquine exerts antitumor effects on NB4 acute promyelocytic leukemia cells and functions synergistically with arsenic trioxide.Oncology letters · 2018Article
- Neddylation, a novel paradigm in liver cancer.Translational gastroenterology and hepatology · 2018Review
- Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor.Molecular cancer therapeutics · 2017Article
- Targeting the overexpressed ROC1 induces G2 cell cycle arrest and apoptosis in esophageal cancer cells.Oncotarget · 2017Article
- Systemic inhibition of neddylation by 3-day MLN4924 treatment regime does not impair autophagic flux in mouse hearts and brains.American journal of cardiovascular disease · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver cancer is the second-most frequent cause of cancer death in the world and is highly treatment resistant. We reported previously that inhibition of neddylation pathway with specific NAE inhibitor MLN4924, suppressed the malignant phenotypes of liver cancer. However, during the process, MLN4924 induces pro-survival autophagy as a mechanism of drug resistance. Here, we report that blockage of autophagy with clinically-available autophagy inhibitors (e.g. chloroquine) significantly enhanced the efficacy of MLN4924 on liver cancer cells by triggering apoptosis. Mechanistically, chloroquine enhanced MLN4924-induced up-regulation of pro-apoptotic proteins (e.g. NOXA) and down-regulation of anti-apoptotic proteins. Importantly, the down-regulation of NOXA expression via siRNA silencing substantially attenuated apoptosis of liver cancer cells. Further mechanistic studies revealed that blockage of autophagy augmented MLN4924-induced DNA damage and reactive oxygen species (ROS) generation. The elimination of DNA damage or blockage of ROS production significantly reduced the expression of NOXA, and thereby attenuated apoptosis and reduced growth inhibition of liver cancer cells. Moreover, blockage of autophagy enhanced the efficacy of MLN4924 in an orthotopic model of human liver cancer, with induction of NOXA and apoptosis in tumor tissues. These findings provide important preclinical evidence for clinical investigation of synergistic inhibition of neddylation and autophagy in liver cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.