ArticleCell death & disease2015
The novel protective role of P27 in MLN4924-treated gastric cancer cells.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 42 citations in OpenAlex.
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- F-box proteins and gastric cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects.International journal of medical sciences · 2024Review
- Role of non-canonical post-translational modifications in gastrointestinal tumors.Cancer cell international · 2023Review
- Targeting NEDD8-activating enzyme for cancer therapy: developments, clinical trials, challenges and future research directions.Journal of hematology & oncology · 2023Review
- Advances in the Application of Preclinical Models in Photodynamic Therapy for Tumor: A Narrative Review.Pharmaceutics · 2023Review
- Targeting cullin neddylation for cancer and fibrotic diseases.Theranostics · 2023Review
- MLN4924 inhibits cell proliferation by targeting the activated neddylation pathway in endometrial carcinoma.The Journal of international medical research · 2021Article
- Hepatic neddylation targets and stabilizes electron transfer flavoproteins to facilitate fatty acid β-oxidation.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Preclinical studies reveal MLN4924 is a promising new retinoblastoma therapy.Cell death discovery · 2020Article
- Circular RNA YAP1 inhibits the proliferation and invasion of gastric cancer cells by regulating the miR-367-5p/p27Molecular cancer · 2018Article
- The dual role of poly(ADP-ribose) polymerase-1 in modulating parthanatos and autophagy under oxidative stress in rat cochlear marginal cells of the stria vascularis.Redox biology · 2018Article
- FAM49B, a novel regulator of mitochondrial function and integrity that suppresses tumor metastasis.Oncogene · 2018Article
- Targeting CAND1 promotes caspase-8/RIP1-dependent apoptosis in liver cancer cells.American journal of translational research · 2018Article
- Combinatorial Screening of Pancreatic Adenocarcinoma Reveals Sensitivity to Drug Combinations Including Bromodomain Inhibitor Plus Neddylation Inhibitor.Molecular cancer therapeutics · 2017Article
- miR-340 Inhibits Proliferation and Induces Apoptosis in Gastric Cancer Cell Line SGC-7901, Possibly via the AKT Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Neddylation inhibitor MLN4924 suppresses growth and migration of human gastric cancer cells.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor-suppressor gene cyclin-dependent kinase inhibitor 1B (P27) is downregulated in gastric cancer cells mainly through proteolytic degradation mediated by the SKP-Cullin1-F-Box (SCF) complex. But the correlation between its downregulation and gastric cancer prognosis still remains indefinite. MLN4924, an anti-tumor agent, which suppresses the SCF complex by inhibiting Cullin1 neddylation, emerges as a promising tool to elucidate its functions in gastric cancer cells. In this study, MLN4924 induced significant growth inhibition of gastric cancer cells in a dose-dependent manner, along with the simultaneous accumulation of P27 and cell cycle abnormalities such as G2/M arrest. Importantly, we found that P27 silencing in MLN4924-treated cells resulted in an enhancement of growth inhibition both in vitro and in vivo. Mechanism analysis revealed the antagonism effects of antioxidants to this excess apoptosis, suggesting reactive oxygen species (ROS) overproduction especially in the mitochondria was the principal cause of the augmentation. Moreover, the robust ROS attacked the mitochondria to initiate collapse of the mitochondrial membrane permeability and the exportation of apoptosis-inducing factor (AIF), IAP-binding mitochondrial protein (SMAC/DIABLO) and cytochrome c. Finally, we also found that P27 knockdown affected the expression profile of several critical BH3 family members to amplify the mitochondrial dysfunction and apoptosis. In summary, our findings unveiled a protective role of P27 by maintaining mitochondrial membrane permeability in MLN4924-treated gastric cancer cells, and therefore highlighted the potential combination of MLN4924 with P27 inhibition to improve its therapeutic efficacy.
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