ArticleOncogene2012
Differential regulation of the two RhoA-specific GEF isoforms Net1/Net1A by TGF-β and miR-24: role in epithelial-to-mesenchymal transition.
Article in Oncogene, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
69 citing papers in PubMed, 112 citations in OpenAlex.
- Conditional Overexpression of Net1 Enhances the Trans-Differentiation of Lgr5Cell proliferation · 2025Article
- Prominosomes - a particular class of extracellular vesicles containing prominin-1/CD133?Journal of nanobiotechnology · 2025Review
- miR-194-3p regulates epithelial-mesenchymal transition in embryonic epicardial cells via p120/β-catenin signaling.Acta biochimica et biophysica Sinica · 2024Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Review
- MANCR lncRNA Modulates Cell-Cycle Progression and Metastasis by Cis-Regulation of NuclearMolecular and cellular biology · 2024Article
- Src stimulates Abl-dependent phosphorylation of the guanine exchange factor Net1A to promote its cytosolic localization and cell motility.The Journal of biological chemistry · 2023Article
- The molecular mechanisms and therapeutic strategies of EMT in tumor progression and metastasis.Journal of hematology & oncology · 2022Review
- MicroRNA expression profiling of endocrine sensitive and resistant breast cancer cell lines.Biochemistry and biophysics reports · 2022Article
- Review
- Epithelial-mesenchymal transition process during embryo implantation.Cell and tissue research · 2022Review
- Role of Small GTPase RhoA in DNA Damage Response.Biomolecules · 2021Review
- A potential Rho GEF and Rac GAP for coupled Rac and Rho cycles during mesenchymal-to-epithelial-like transitions.Small GTPases · 2021Article
- MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.Cancers · 2020Review
- TGF-β Signaling.Biomolecules · 2020Review
- Mechanical tumor microenvironment and transduction: cytoskeleton mediates cancer cell invasion and metastasis.International journal of biological sciences · 2020Review
- Connecting sex differences, estrogen signaling, and microRNAs in cardiac fibrosis.Journal of molecular medicine (Berlin, Germany) · 2019Review
- Review
- miR-24 Is Elevated in Ulcerative Colitis Patients and Regulates Intestinal Epithelial Barrier Function.The American journal of pathology · 2019Article
- Participation of the SMAD2/3 signalling pathway in the down regulation of megalin/LRP2 by transforming growth factor beta (TGF-ß1).PloS one · 2019Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the present study we analyzed the regulation of the two isoforms of the RhoA-specific guanine nucleotide exchange factor Net1 by transforming growth factor-β (TGF-β) in keratinocytes. We report that short-term TGF-β treatment selectively induced Net1 isoform2 (Net1A) but not Net1 isoform1. This led to upregulation of cytoplasmic Net1A protein levels that were necessary for TGF-β-mediated RhoA activation. Smad signaling and the MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway were involved in Net1A upregulation by TGF-β. Interestingly, long-term TGF-β treatment resulted in Net1 mRNA downregulation and Net1A protein degradation by the proteasome. Furthermore, we identified the microRNA miR-24 as a novel post-transcriptional regulator of Net1A expression. Silencing of Net1A resulted in disruption of E-cadherin- and zonula occludens-1 (ZO-1)-mediated junctions, as well as expression of the transcriptional repressor of E-cadherin, Slug and the mesenchymal markers N-cadherin, plasminogen activator inhibitor-1 (PAI-1) and fibronectin, indicating that late TGF-β-induced downregulation of Net1A is involved in epithelial-to-mesenchymal transition (EMT). Finally, miR-24 was found to be implicated in the regulation of the EMT program in response to TGF-β and was shown to be directly involved in the TGF-β-induced breast cancer cell invasiveness through Net1A regulation. Our results emphasize the importance of Net1 isoform2 in the short- and long-term TGF-β-mediated regulation of EMT.
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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.