ArticleCell death & disease2023
Loss of function of GATA3 regulates FRA1 and c-FOS to activate EMT and promote mammary tumorigenesis and metastasis.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 49 citations in OpenAlex.
- Tumor Electric Field Therapy Inhibits Epithelial-Mesenchymal Transition, Invasion, and Migration of Glioblastoma by Targeting the c-FOS/CXCL14 Axis.CNS neuroscience & therapeutics · 2026Article
- FOS drives podocyte injury and renal fibrosis in diabetic kidney disease via direct Smad3 binding.Cellular and molecular life sciences : CMLS · 2026Article
- CXCL12/ZNF503/GATA3/MMP1 axis promotes tumor progression and metastasis of triple-negative breast cancer.Breast cancer research : BCR · 2026Article
- Pioneering new enhancers by GATA3: role of facilitating transcription factors and chromatin remodeling.Nucleic acids research · 2025Article
- Investigation of c-Fos/c-Jun Signaling Pathways in Periostracum Cicadae's Inhibition of EMT in Gastric Tissue.Pharmaceuticals (Basel, Switzerland) · 2025Article
- C-FOS promotes the formation of neutrophil extracellular traps and the recruitment of neutrophils in lung metastasis of triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- ROR1 facilitates glioblastoma growth via stabilizing GRB2 to promote c-Fos expression in glioma stem cells.Neuro-oncology · 2025Article
- Integrated Network Pharmacology, Machine Learning and Experimental Validation to Identify the Key Targets and Compounds ofOncoTargets and therapy · 2025Article
- Article
- Non-coding RNAs as key regulators of epithelial-mesenchymal transition in breast cancer.Frontiers in cell and developmental biology · 2025Review
- RNA Sequencing Identifies Novel Signaling Pathways and Potential Drug Target Genes Induced by FOSL1 in Glioma Progression and Stemness.Biologics : targets & therapy · 2025Article
- FRA1 (Frontiers in cell and developmental biology · 2025Article
- Investigation of exJSRV LTR promoter activity based on transcription factor regulatory networks.Frontiers in veterinary science · 2025Article
- Transcriptomic analysis reveals the key role of inflammatory and immune signaling in the anti-perimenopausal depression effects of Bushen Shugan Huayu decoction.Frontiers in psychiatry · 2025Article
- Silencing PPAP2C inhibits lung adenocarcinoma migration and invasion via the ERK/JNK pathway.Molecular medicine reports · 2025Article
- Epigenetic activation of JAG1 by AID contributes to metastasis of hepatocellular carcinoma.The Journal of biological chemistry · 2025Article
- Review
- Single-cell data revealed the regulatory mechanism of TNK cell heterogeneity in liver metastasis from gastric cancer.Discover oncology · 2024Article
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- Interaction of NF-κB and FOSL1 drives glioma stemness.Cellular and molecular life sciences : CMLS · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Basal-like breast cancers (BLBCs) are among the most aggressive cancers, partly due to their enrichment of cancer stem cells (CSCs). Breast CSCs can be generated from luminal-type cancer cells via epithelial-mesenchymal transition (EMT). GATA3 maintains luminal cell fate, and its expression is lost or reduced in BLBCs. However, deletion of Gata3 in mice or cells results in early lethality or proliferative defects. It is unknown how loss-of-function of GATA3 regulates EMT and CSCs in breast cancer. We report here that haploid loss of Gata3 in mice lacking p18Ink4c, a cell cycle inhibitor, up-regulates Fra1, an AP-1 family protein that promotes mesenchymal traits, and downregulates c-Fos, another AP-1 family protein that maintains epithelial fate, leading to activation of EMT and promotion of mammary tumor initiation and metastasis. Depletion of Gata3 in luminal tumor cells similarly regulates Fra1 and c-Fos in activation of EMT. GATA3 binds to FOSL1 (encoding FRA1) and FOS (encoding c-FOS) loci to repress FOSL1 and activate FOS transcription. Deletion of Fra1 or reconstitution of Gata3, but not reconstitution of c-Fos, in Gata3 deficient tumor cells inhibits EMT, preventing tumorigenesis and/or metastasis. In human breast cancers, GATA3 expression is negatively correlated with FRA1 and positively correlated with c-FOS. Low GATA3 and FOS, but high FOSL1, are characteristics of BLBCs. Together, these data provide the first genetic evidence indicating that loss of function of GATA3 in mammary tumor cells activates FOSL1 to promote mesenchymal traits and CSC function, while concurrently repressing FOS to lose epithelial features. We demonstrate that FRA1 is required for the activation of EMT in GATA3 deficient tumorigenesis and metastasis.
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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 Socratic graph.