ArticlePloS one2016
BMP4 Signaling Is Able to Induce an Epithelial-Mesenchymal Transition-Like Phenotype in Barrett's Esophagus and Esophageal Adenocarcinoma through Induction of SNAIL2.
Article in PloS one, 2016. 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 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- The Interplay Between Esophageal Adenocarcinoma and Its Tumor Microenvironment: Toward Innovative Therapies.Cells · 2025Review
- LncRNA small nucleolar RNA host gene 1 (SNHG1) mediates acidic bile salt-induced EMT via the ULK1-Notch1 axis in Barrett's esophagus.Molecular biomedicine · 2025Article
- The mechanism of high mobility group box-1 in the proliferation and macrophage polarization in esophageal squamous cell carcinoma cells.European journal of medical research · 2025Article
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- Single Cell Sequencing Reveals Mechanisms of Persistent Truncus Arteriosus Formation afterGenes · 2022Article
- Selective targeting BMP2 and 4 in SMAD4 negative esophageal adenocarcinoma inhibits tumor growth and aggressiveness in preclinical models.Cellular oncology (Dordrecht, Netherlands) · 2022Article
- COX-2 strengthens the effects of acid and bile salts on human esophageal cells and Barrett esophageal cells.BMC molecular and cell biology · 2022Article
- Identification of Molecular Subtypes and Potential Small-Molecule Drugs for Esophagus Cancer Treatment Based on mJournal of oncology · 2022Article
- Multivariate gene expression-based survival predictor model in esophageal adenocarcinoma.Thoracic cancer · 2020Article
- Detection of circulating BMP5 as a risk factor for Barrett's esophagus.Scientific reports · 2020Article
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- Chromosome 19 microRNA cluster enhances cell reprogramming by inhibiting epithelial-to-mesenchymal transition.Scientific reports · 2020Article
- Collision tumors of the lung: A case report of urothelial carcinoma metastasizing to renal cell carcinoma with heterotopic ossification.Respiratory medicine case reports · 2020Article
- From genetics to signaling pathways: molecular pathogenesis of esophageal adenocarcinoma.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Stromal regulation of prostate cancer cell growth by mevalonate pathway enzymes HMGCS1 and HMGCR.Oncology letters · 2017Article
- MiR-876-5p suppresses epithelial-mesenchymal transition of lung cancer by directly down-regulating bone morphogenetic protein 4.Journal of biosciences · 2017Article
- Evaluation of pancreatic cancer cell migration with multiple parameters in vitro by using an optical real-time cell mobility assay device.BMC cancer · 2017Article
- The characterization of an intestine-like genomic signature maintained during Barrett's-associated adenocarcinogenesis reveals an NR5A2-mediated promotion of cancer cell survival.Scientific reports · 2016Article
- MicroRNAs as Potential Targets for Therapeutic Intervention With Metastasis of Non-small Cell Lung Cancer.Cancer genomics & proteomicsReview
- Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBone morphogenetic protein 4 (BMP4) signaling is involved in the development of Barrett's esophagus (BE), a precursor of esophageal adenocarcinoma (EAC). In various cancers, BMP4 has been found to induce epithelial-mesenchymal transition (EMT) but its function in the development of EAC is currently unclear.
aimTo investigate the expression of BMP4 and several members of the BMP4 pathway in EAC. Additionally, to determine the effect of BMP4 signaling in a human Barrett's esophagus (BAR-T) and adenocarcinoma (OE33) cell line.
methodsExpression of BMP4, its downstream target ID2 and members of the BMP4 pathway were determined by Q-RT-PCR, immunohistochemistry and Western blot analysis using biopsy samples from EAC patients. BAR-T and OE33 cells were incubated with BMP4 or the BMP4 antagonist, Noggin, and cell viability and migration assays were performed. In addition, expression of factors associated with EMT (SNAIL2, CDH1, CDH2 and Vimentin) was evaluated by Q-RT-PCR and Western blot analysis.
resultsCompared to squamous epithelium (SQ), BMP4 expression was significantly upregulated in EAC and BE. In addition, the expression of ID2 was significantly upregulated in EAC and BE compared to SQ. Western blot analysis confirmed our results, showing an upregulated expression of BMP4 and ID2 in both BE and EAC. In addition, more phosphorylation of SMAD1/5/8 was observed. BMP4 incubation inhibited cell viability, but induced cell migration in both BAR-T and OE33 cells. Upon BMP4 incubation, SNAIL2 expression was significantly upregulated in BAR-T and OE33 cells while CDH1 expression was significantly downregulated. These results were confirmed by Western blot analysis.
conclusionOur results indicate active BMP4 signaling in BE and EAC and suggest that this results in an invasive phenotype by inducing an EMT-like response through upregulation of SNAIL2 and subsequent downregulation of CDH1.
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