ArticleCell communication and signaling : CCS2023
GRHL2-controlled gene expression networks in luminal breast cancer.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Comparative Transcriptomics Suggests that Breast Secretory Epithelium Reuses Gene Repertoires Conserved Across Vertebrates Beyond Mammals.Genome biology and evolution · 2026Article
- Defining the DNA Binding Specificity of GRHL2.bioRxiv : the preprint server for biology · 2026Article
- KMT2C and KMT2D amplify GRHL2-driven enhancer activation.bioRxiv : the preprint server for biology · 2026Article
- Mechanistic dissection of GRHL2 and PR transcriptional co-regulation in breast cells.PLoS genetics · 2026Article
- Phosphorylation-dependent modulation of the Lamin A/C-EZH2 complex regulates epithelial-mesenchymal plasticity.Nucleic acids research · 2026Article
- Elevated Epithelial Splicing Regulatory Protein 1 Expression in Biliary Atresia Indicates Its Potential as a Molecular Marker.Biomolecules · 2025Article
- Derepression of the epithelial transcription factor GRHL2 promotes direct hepatocyte-to-cholangiocyte transdifferentiation.PLoS biology · 2025Article
- Machine learning multiomics Deciphers GRHL2 associated tumor microenvironment evolution guiding precision therapeutics in breast cancer.Discover oncology · 2025Article
- Contrasting roles of KMT2C and KMT2D in breast cancer.Scientific reports · 2025Article
- Article
- Transcriptional programs of cell identity and p53-induced stress responses are associated with distinctive features of spatial genome organization.Nucleic acids research · 2025Article
- Epigenetic regulation of nuclear receptors: Implications for endocrine-related diseases and therapeutic strategies.Genes & diseases · 2025Review
- MORF4L2 induces immunosuppressive microenvironment and immunotherapy resistance through GRHL2/MORF4L2/H4K12Ac/CSF1 axis in triple-negative breast cancer.Biomarker research · 2025Article
- Article
- GRHL2 regulates keratinocyte EMT-MET dynamics and scar formation during cutaneous wound healing.Cell death & disease · 2024Article
- Re-analysis of single cell and spatial transcriptomics data reveals B cell landscape in gastric cancer microenvironment and its potential crosstalk with tumor cells for clinical prognosis.Journal of translational medicine · 2024Article
- Article
- GRHL2 suppression of NT5E/CD73 in breast cancer cells modulates CD73-mediated adenosine production and T cell recruitment.iScience · 2024Article
- Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance.Cancer metastasis reviews · 2024Review
- Placental co-transcriptional activator Vestigial-like 1 (VGLL1) drives tumorigenesis via increasing transcription of proliferation and invasion genes.Frontiers in oncology · 2024Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Grainyhead like 2 (GRHL2) is an essential transcription factor for development and function of epithelial tissues. It has dual roles in cancer by supporting tumor growth while suppressing epithelial to mesenchymal transitions (EMT). GRHL2 cooperates with androgen and estrogen receptors (ER) to regulate gene expression. We explore genome wide GRHL2 binding sites conserved in three ER⍺/GRHL2 positive luminal breast cancer cell lines by ChIP-Seq. Interaction with the ER⍺/FOXA1/GATA3 complex is observed, however, only for a minor fraction of conserved GRHL2 peaks. We determine genome wide transcriptional dynamics in response to loss of GRHL2 by nascent RNA Bru-seq using an MCF7 conditional knockout model. Integration of ChIP- and Bru-seq pinpoints candidate direct GRHL2 target genes in luminal breast cancer. Multiple connections between GRHL2 and proliferation are uncovered, including transcriptional activation of ETS and E2F transcription factors. Among EMT-related genes, direct regulation of CLDN4 is corroborated but several targets identified in other cells (including CDH1 and ZEB1) are ruled out by both ChIP- and Bru-seq as being directly controlled by GRHL2 in luminal breast cancer cells. Gene clusters correlating positively (including known GRHL2 targets such as ErbB3, CLDN4/7) or negatively (including TGFB1 and TGFBR2) with GRHL2 in the MCF7 knockout model, display similar correlation with GRHL2 in ER positive as well as ER negative breast cancer patients. Altogether, this study uncovers gene sets regulated directly or indirectly by GRHL2 in luminal breast cancer, identifies novel GRHL2-regulated genes, and points to distinct GRHL2 regulation of EMT in luminal breast cancer cells. Video Abstract.
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