ArticleOncoTargets and therapy2019
MDM2 promotes epithelial-mesenchymal transition through activation of Smad2/3 signaling pathway in lung adenocarcinoma.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Topotecan Synergizes with SP141 in the Management of Uveal Melanoma.bioRxiv : the preprint server for biology · 2026Article
- Discovery of Benzophenanthridine Alkaloids fromPharmaceuticals (Basel, Switzerland) · 2026Article
- High-throughput strategy for targeting MDM2 in uveal melanoma to reverse radiation therapy resistance.Cell death discovery · 2026Article
- Glucocorticoid inhibits lung cancer cells proliferation and migration by suppressing smad2/3 activation.Scientific reports · 2025Article
- Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- Functional role and epithelial to mesenchymal transition of the miR-590-3p/MDM2 axis in hepatocellular carcinoma.BMC cancer · 2023Article
- Expression and Clinical Significance of MDM2 in Non-Functioning PitNETs.Medicina (Kaunas, Lithuania) · 2023Article
- CircRNA PVT1 modulated cell migration and invasion through Epithelial-Mesenchymal Transition (EMT) mediation in gastric cancer through miR-423-5p/Smad3 pathway.Regenerative therapy · 2022Article
- Functional interaction between S100A1 and MDM2 may modulate p53 signaling in normal and malignant endometrial cells.BMC cancer · 2022Article
- Silencing of kallikrein-related peptidase 6 attenuates the proliferation, migration, and invasion of gastric cancer cells through inhibition of epithelial-mesenchymal transition.Experimental and therapeutic medicine · 2021Article
- Article
- Regulation of Epithelial-Mesenchymal Plasticity by the E3 Ubiquitin-Ligases in Cancer.Cancers · 2020Review
- Roles of DANCR/microRNA-518a-3p/MDMA ceRNA network in the growth and malignant behaviors of colon cancer cells.BMC cancer · 2020Article
- Long non-coding RNA XIST expedites lung adenocarcinoma progression through upregulating MDM2 expression via binding to miR-363-3p.Thoracic cancer · 2020Article
- STRIP2, a member of the striatin-interacting phosphatase and kinase complex, is implicated in lung adenocarcinoma cell growth and migration.FEBS open bio · 2020Article
- High expression of keratin 6C is associated with poor prognosis and accelerates cancer proliferation and migration by modulating epithelial-mesenchymal transition in lung adenocarcinoma.Genes & genomics · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMouse double minute 2 (MDM2) contributes to cancer metastasis and epithelial-mesenchymal transition (EMT). This study aimed to investigate small mothers against decapentaplegic (Smad) signaling in MDM2-mediated EMT in lung adenocarcinoma (LAC). MATERIALS AND
methodsExpression patterns of MDM2 in LAC tissues, adjacent tissues, and cell lines (BEAS-2B, PC9, H1975, and A549) were detected. We then overexpressed MDM2 in PC9 cells and knocked it down in H1975 cells. To explore whether MDM2 activates EMT through the Smad2/3 signaling pathway, Smad2 and Smad3 were also silenced by siRNA in H1975 cells. Male BALB/c nude mice were used in in vivo model to validate the effects of MDM2 on LAC cells.
resultsMDM2 was significantly upregulated in LAC tissues compared with adjacent tissues. The expression of MDM2 was relatively higher in PC9 cells and relatively lower in H1975 cells compared with A549 cells. Overexpression of MDM2 significantly increased cell proliferation, migration, and invasion in LAC cells, while inhibiting apoptosis in PC9 cells. On the contrary, silencing of MDM2 significantly inhibited the expression of EMT-related genes N-cadherin and vimentin, while promoting the expression of E-cadherin and β-catenin. In vivo, MDM2 knockdown inhibited tumor growth. In addition, the expression of Smad2/3 was correlated with MDM2 in H1975 cells transfected with Smad2 and Smad3 siRNAs, which inhibited EMT progress.
conclusionMDM2 can activate the Smad2/3 signaling pathway, which promotes the proliferation and EMT progress of LAC cells.
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