ArticlePloS one2015
The Disintegrin and Metalloprotease ADAM12 Is Associated with TGF-β-Induced Epithelial to Mesenchymal Transition.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- The Role of Distinct Cancer-Associated Fibroblast Subtypes in Prostate Cancer Immunotherapy.International journal of biological sciences · 2026Review
- Unveiling the significance of ADAM12 through pan-cancer analysis and experimental verification in gastric cancer.Discover oncology · 2025Article
- Review
- A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition.International journal of oncology · 2023Article
- Identification of the circRNA-miRNA-mRNA Regulatory Network in Pterygium-Associated Conjunctival Epithelium.BioMed research international · 2022Article
- Article
- Key metalloproteinase-mediated pathways in the kidney.Nature reviews. Nephrology · 2021Review
- A Disintegrin and Metalloprotease 12 Promotes Tumor Progression by Inhibiting Apoptosis in Human Colorectal Cancer.Cancers · 2021Article
- ADAM and ADAMTS Proteins, New Players in the Regulation of Hepatocellular Carcinoma Microenvironment.Cancers · 2021Review
- Cell morphology and mechanosensing can be decoupled in fibrous microenvironments and identified using artificial neural networks.Scientific reports · 2021Article
- Cancer Stem Cells-Key Players in Tumor Relapse.Cancers · 2021Review
- Inflammatory Mediators in Oral Cancer: Pathogenic Mechanisms and Diagnostic Potential.Frontiers in oral health · 2021Review
- Association of Mps one binder kinase activator 1 (MOB1) expression with poor disease-free survival in individuals with non-small cell lung cancer.Thoracic cancer · 2020Article
- Transcriptional analysis of cleft palate in TGFβ3 mutant mice.Scientific reports · 2020Article
- Rab27a plays a dual role in metastatic propensity of pancreatic cancer.Scientific reports · 2020Article
- ADAM12 is A Potential Therapeutic Target Regulated by Hypomethylation in Triple-Negative Breast Cancer.International journal of molecular sciences · 2020Article
- ADAM9 Mediates Triple-Negative Breast Cancer Progression via AKT/NF-κB Pathway.Frontiers in medicine · 2020Article
- COX2 is induced in the ovarian epithelium during ovulatory wound repair and promotes cell survival†.Biology of reproduction · 2019Article
- A novel miRNA-4484 is up-regulated on microarray and associated with increased MMP-21 expression in serum of systemic sclerosis patients.Scientific reports · 2019Article
- Observational
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increased expression of the Disintegrin and Metalloprotease ADAM12 has been associated with human cancers, however its role remain unclear. We have previously reported that ADAM12 expression is induced by the transforming growth factor, TGF-β and promotes TGF-β-dependent signaling through interaction with the type II receptor of TGF-β. Here we explore the implication of ADAM12 in TGF-β-mediated epithelial to mesenchymal transition (EMT), a key process in cancer progression. We show that ADAM12 expression is correlated with EMT markers in human breast cancer cell lines and biopsies. Using a non-malignant breast epithelial cell line (MCF10A), we demonstrate that TGF-β-induced EMT increases expression of the membrane-anchored ADAM12L long form. Importantly, ADAM12L overexpression in MCF10A is sufficient to induce loss of cell-cell contact, reorganization of actin cytoskeleton, up-regulation of EMT markers and chemoresistance. These effects are independent of the proteolytic activity but require the cytoplasmic tail and are specific of ADAM12L since overexpression of ADAM12S failed to induce similar changes. We further demonstrate that ADAM12L-dependent EMT is associated with increased phosphorylation of Smad3, Akt and ERK proteins. Conversely, inhibition of TGF-β receptors or ERK activities reverses ADAM12L-induced mesenchymal phenotype. Together our data demonstrate that ADAM12L is associated with EMT and contributes to TGF-β-dependent EMT by favoring both Smad-dependent and Smad-independent pathways.
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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.