ArticleBritish journal of cancer2017
MDM2 promotes epithelial-mesenchymal transition and metastasis of ovarian cancer SKOV3 cells.
Article in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 55 papers.
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55 citing papers in PubMed, 98 citations in OpenAlex.
- hsa_circ_0008758 Activates the MDM2/FOXO3a/PGK1 Pathway Through the miR-361-3p/SPIN1 Axis to Promote the Warburg Effect of Non-Small Cell Lung Cancer.Tissue engineering and regenerative medicine · 2026Article
- The miR-16-1-3p suppresses proliferation and invasiveness via the MDM2-p53 axis in TGF-β1 signaling in osteosarcoma.Molecular therapy. Oncology · 2026Article
- Helicobacter pylori Lipopolysaccharide Upregulates MDM2 via the TLR4/MAPK/AP-1 Pathway to Promote Gastric Cancer Progression.Digestive diseases and sciences · 2026Article
- Histone acetyltransferase HBO1 in cancer biology: Essential mechanisms and implications for targeted therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Regulatory mechanisms for Snail protein stability: ubiquitin-proteasome system and chaperone-mediated autophagy.Experimental & molecular medicine · 2026Review
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53.Nature communications · 2024Article
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Anoikis related genes may be novel markers associated with prognosis for ovarian cancer.Scientific reports · 2024Article
- Targeted inhibition of the ATR/CHK1 pathway overcomes resistance to olaparib and dysregulates DNA damage response protein expression in BRCA2Scientific reports · 2023Article
- Logic-based modeling and drug repurposing for the prediction of novel therapeutic targets and combination regimens against E2F1-driven melanoma progression.BMC chemistry · 2023Article
- The Analysis of Selected miRNAs and TargetBiomedicines · 2023Article
- The synergistic effect of EMT regulators and m6A modification on prognosis-related immunological signatures for ovarian cancer.Scientific reports · 2023Article
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- CLDN6 Suppresses Migration and Invasion of MCF-7 and SKBR-3 Breast Cancer Cells by Blocking the SMAD/Snail/MMP-2/9 Axis.Bulletin of experimental biology and medicine · 2023Article
- Article
- Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma.BMC cancer · 2023Article
- An EMT-based gene signature enhances the clinical understanding and prognostic prediction of patients with ovarian cancers.Journal of ovarian research · 2023Article
- Targeting MDM4 as a Novel Therapeutic Approach in Prostate Cancer Independent of p53 Status.Cancers · 2022Article
- MAGED2 Is Required under Hypoxia for cAMP Signaling by Inhibiting MDM2-Dependent Endocytosis of G-Alpha-S.Cells · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetastasis accounts for the most lethal reason for the death of ovarian cancer patients, but remains largely untreated. Epithelial-mesenchymal transition (EMT) is critical for the conversion of early-stage ovarian tumours into metastatic malignancies. Thus the exploration of the signalling pathways promoting EMT would open potential opportunities for the treatment of metastatic ovarian cancer. Herein, the putative role of MDM2 in regulating EMT and metastasis of ovarian cancer SKOV3 cells was investigated.
methodsThe regulatory effects by MDM2 on cell motility was emulated by wound-healing and transwell assays. The effects on EMT transition and Smad pathway were studied by depicting the expression levels of epithelial marker E-cadherin as well as key components of Smad pathway. To evaluate the clinical relevance of our findings, the correlation of MDM2 expression levels with the stages of 104 ovarian cancer patients was investigated by immunohistochemistry assay.
resultsWe demonstrate that MDM2 functions as a key factor to drive EMT and motility of ovarian SKOV3 cells, by facilitating the activation of TGF-β-Smad pathway, which results in the increased transcription of snail/slug and the subsequent loss of E-cadherin levels. Such induction of EMT is sustained in either E3 ligase-depleted MDM2 or E3 ligase inhibitor HLI-373-treated cells, while being impaired by the N-terminal deletion of MDM2, which is also reflected by the inhibitory effects against EMT by Nutlin-3a, the N-terminal targeting agent. The expression levels of MDM2 is highly correlated with the stages of the ovarian cancer patients, and the higher expression of MDM2 together with TGFB are closely correlated with poor prognosis and predict a high risk of ovarian cancer patients.
conclusionsThis study suggests that MDM2 activates Smad pathway to promote EMT in ovarian cancer metastasis, and targeting the N-terminal of MDM2 can reprogram EMT and impede the mobility of cancer cells.
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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.