ArticleThe Journal of biological chemistry2013
Dual roles of the transcription factor grainyhead-like 2 (GRHL2) in breast cancer.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 137 citations in OpenAlex.
- Intrinsic cellular heterogeneity directs divergent epithelial-to-mesenchymal transition outcomes.The FEBS journal · 2026Article
- Fluctuating environment causes neoplastic transition and epithelial-mesenchymal plasticity in human cells.Research square · 2026Article
- Defining the DNA Binding Specificity of GRHL2.bioRxiv : the preprint server for biology · 2026Article
- Phosphorylation-dependent modulation of the Lamin A/C-EZH2 complex regulates epithelial-mesenchymal plasticity.Nucleic acids research · 2026Article
- Derepression of the epithelial transcription factor GRHL2 promotes direct hepatocyte-to-cholangiocyte transdifferentiation.PLoS biology · 2025Article
- Enhancer Reprogramming Reveals the Tumorigenic Role of PTPRZ1 in Lung Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Identification of copper related biomarkers in breast cancer using machine learning.Discover oncology · 2025Article
- Association Analysis of SNPs inAnimals : an open access journal from MDPI · 2025Article
- MORF4L2 induces immunosuppressive microenvironment and immunotherapy resistance through GRHL2/MORF4L2/H4K12Ac/CSF1 axis in triple-negative breast cancer.Biomarker research · 2025Article
- Article
- Grainyhead-like-2, an epithelial master programmer, promotes interferon induction and suppresses breast cancer recurrence.Molecular immunology · 2024Article
- GRHL2 suppression of NT5E/CD73 in breast cancer cells modulates CD73-mediated adenosine production and T cell recruitment.iScience · 2024Article
- Identification of miR-6794-3p as a suppressor in pancreatic cancer metastasis.International journal of biological sciences · 2024Article
- Prognostic value of blood GRHL2 in patients with non-small-cell lung cancer after radiotherapy and chemotherapy.Biomarkers in medicine · 2024Article
- Exploration of the Correlation BetweenPharmacogenomics and personalized medicine · 2024Article
- E74‑like ETS transcription factor 5 facilitates cell proliferation through regulating the expression of adenomatous polyposis coli 2 in non‑small cell lung cancer.International journal of molecular medicine · 2023Article
- Silencing ofOncology letters · 2023Article
- The Transcriptional and Epigenetic Landscape of Cancer Cell Lineage Plasticity.Cancer discovery · 2023Review
- GRHL2 Regulation of Growth/Motility Balance in Luminal versus Basal Breast Cancer.International journal of molecular sciences · 2023Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Using a retrovirus-mediated cDNA expression cloning approach, we identified the grainyhead-like 2 (GRHL2) transcription factor as novel protooncogene. Overexpression of GRHL2 in NIH3T3 cells induced striking morphological changes, an increase in cell proliferation, anchorage-independent growth, and tumor growth in vivo. By combining a microarray analysis and a phylogenetic footprinting analysis with various biochemical assays, we identified the epidermal growth factor receptor family member Erbb3 as a novel GRHL2 target gene. In breast cancer cell lines, shRNA-mediated knockdown of GRHL2 expression or functional inactivation of GRHL2 using dominant negative GRHL2 proteins induces down-regulation of ERBB3 gene expression, a striking reduction in cell proliferation, and morphological and phenotypical alterations characteristic of an epithelial-to-mesenchymal transition (EMT), thus implying contradictory roles of GRHL2 in breast carcinogenesis. Interestingly, we could further demonstrate that expression of GRHL2 is directly suppressed by the transcription factor zinc finger enhancer-binding protein 1 (ZEB1), which in turn is a direct target for repression by GRHL2, suggesting that the EMT transcription factors GRHL2 and ZEB1 form a double negative regulatory feedback loop in breast cancer cells. Finally, a comprehensive immunohistochemical analysis of GRHL2 expression in primary breast cancers showed loss of GRHL2 expression at the invasive front of primary tumors. A pathophysiological relevance of GRHL2 in breast cancer metastasis is further demonstrated by our finding of a statistically significant association between loss of GRHL2 expression in primary breast cancers and lymph node metastasis. We thus demonstrate a crucial role of GRHL2 in breast carcinogenesis.
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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 OpenQuestion graph.