ArticleNeoplasia (New York, N.Y.)2017
Inhibition of Neddylation Modification Sensitizes Pancreatic Cancer Cells to Gemcitabine.
Article in Neoplasia (New York, N.Y.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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
14 citing papers in PubMed, 24 citations in OpenAlex.
- RNF187 neddylation in pancreatic cancer activates malignancy via IQGAP1-dependent actin cytoskeleton rearrangement.Oncogene · 2026Article
- Machine Learning-Derived Neddylation Gene Signature for Predicting Prognosis and Immunotherapy Benefits in Colorectal Cancer.ImmunoTargets and therapy · 2025Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- PD-L1 induction via the MEK-JNK-AP1 axis by a neddylation inhibitor promotes cancer-associated immunosuppression.Cell death & disease · 2022Article
- Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo.Biomedicines · 2022Article
- Pevonedistat Suppresses Pancreatic Cancer GrowthFrontiers in oncology · 2022Article
- Impact of posttranslational modifications in pancreatic carcinogenesis and treatments.Cancer metastasis reviews · 2021Review
- The Scribble family in cancer: twentieth anniversary.Oncogene · 2020Review
- Chemogenomic study of gemcitabine using Saccharomyces cerevisiae as model cell-molecular insights about chemoresistance.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2020Article
- Pevonedistat (MLN4924): mechanism of cell death induction and therapeutic potential in colorectal cancer.Cell death discovery · 2020Article
- An overactive neddylation pathway serves as a therapeutic target and MLN4924 enhances the anticancer activity of cisplatin in pancreatic cancer.Oncology letters · 2019Article
- Inhibition of neddylation modification by MLN4924 sensitizes hepatocellular carcinoma cells to sorafenib.Oncology reports · 2019Article
- Protein neddylation and its alterations in human cancers for targeted therapy.Cellular signalling · 2018Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA with a 5-year survival rate less than 3% to 5%. Gemcitabine remains as a standard care for PDAC patients. Although protein neddylation is abnormally activated in many human cancers, whether neddylation dysregulation is involved in PDAC and whether targeting neddylation would sensitize pancreatic cancer cells to gemcitabine remain elusive. Here we report that high expression of neddylation components, NEDD8 and NAE1, are associated with poor survival of PDAC patients. Blockage of neddylation by MLN4924, a small molecule inhibitor targeting this modification, significantly sensitizes pancreatic cancer cells to gemcitabine, as evidenced by reduced growth both in monolayer culture and soft agar, reduced clonogenic survival, decreased invasion capacity, increased apoptosis, G2/M arrest, and senescence. Importantly, combinational treatment of MLN4924-gemcitabine near completely suppressed in vivo growth of pancreatic cancer cells. Mechanistically, accumulation of NOXA, a pro-apoptotic protein and ERBIN, a RAS signal inhibitor, appears to play, at least in part, a causal role in MLN4924 chemo-sensitization. Our study demonstrates that neddylation modification is a valid target for PDAC, and provides the proof-of-concept evidence for future clinical trial of MLN4924-gemcitabine combination for the treatment of pancreatic cancer patients.
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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.