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In this study, we demonstrated for the first time that GRHL2 has a functional role in the regulation of epithelial plasticity of PDAC cells.
data analysis and modeling results highlight the relationships among multiple crucial Epithelial-to-Mesenchymal Transition /Mesenchymal-to-Epithelial Transition drivers including ZEB1, GRHL2, CD24 (show CD24 Proteins), and ESRP1 (show ESRP1 Proteins), particularly in basal-like breast cancers, which are most similar to triple-negative breast cancer (TNBC) and are considered the most dangerous subtype
Data indicate a 'phenotypic stability factors' (PSFs) such as GRHL2 that couple to the core epithelial-to-mesenchymal transition (EMT) decision-making circuit (miR-200/ZEB) and stabilize hybrid epithelial/mesenchymal (hybrid E/M) E/M phenotype.
All of these processes involve epithelial-mesencyhmal transition (EMT (show ITK Proteins)), MET or a sequence of both, suggesting that the GRHL (show GHRL Proteins) factors((GRHL1 (show GRHL1 Proteins), GRHL2 and GRHL3 (show GRHL3 Proteins)), could potentially affect tumor initiation and progression via EMT (show ITK Proteins)
Silencing of GRHL2 expression in non-tumorigenic kidney cell line results in increased cell proliferation, increased resistance to apoptosis, as well as changes in the levels of selected proteins involved in the pathogenesis of clear cell renal cell carcinoma (show MOK Proteins) (ccRCC). These changes support the potential role for GRHL2 as a suppressor of ccRCC.
Results demonstrate a mechanistic role for GRHL2 in promoting anoikis through metabolic alterations.
GRHL2 maintained AR expression in multiple prostate cancer model systems, was required for cell proliferation, enhanced AR's transcriptional activity, and colocated with AR at specific sites on chromatin to regulate genes relevant to disease progression.
Studies indicate that Grainyhead-like transcription factor 2 (show HNF1B Proteins) (GRHL2) controls the expression of E-cadherin (CDH1 (show CDH1 Proteins)) required for adherens junctions and possibly regulates the expression of claudin-4 (CLDN4 (show CLDN4 Proteins)) in tight junctions.
results indicated GRHL2 might be a noise-induced hearing loss (NIHL) susceptibility gene, but the effect of POU4F3 (show POU4F3 Proteins) on NIHL could only be detected when taking noise exposure into account and their effects were enhanced by higher levels of noise exposure
These data are indicative for a strong oncogenic potential of the GRHL2 gene in epithelial ovarian cancer cells displaying either epithelial (A2780s) or mesenchymal (SKOV3) phenotypes.
Results indicate GRHL2 as a novel progenitor cell maker in the developing pituitary that may contribute to progenitor cell function and maintenance.
GRHL2 promotes the epithelial nature of non-neural ectoderm during dynamic events of neural tube formation by both activating key epithelial genes and actively suppressing epithelial-mesenchymal (EMT (show ITK Proteins)) transition through novel downstream EMT (show ITK Proteins) suppressors.
a Grhl2/Ovol2 (show OVOL2 Proteins) network controls Cldn4 (show CLDN4 Proteins) and Rab25 (show RAB25 Proteins) expression that facilitates lumen expansion and barrier formation in subtypes of renal epithelia
Our findings reveal important pathophysiological differences between human pulmonary fibrosis and specific mouse models of fibrosis and support a crucial role of GRHL2 in epithelial activation in lung fibrosis and perhaps also in epithelial plasticity.
expression of GRHL2 is directly suppressed by the 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
Grhl2 plays an essential role in the determination of epithelial phenotype of breast cancers, EMT (show ITK Proteins) and tumor progression
the results indicate that Grhl2 regulates epithelial morphogenesis through transcriptional up-regulation of Cldn3 (show CLDN3 Proteins) and Cldn4 (show CLDN4 Proteins), as well as of Rab25 (show RAB25 Proteins), which increases the Cldn4 (show CLDN4 Proteins) protein and its localization at TJs
Grhl2 and Nkx2-1 (show NKX2-1 Proteins) bind to each other's promoter in vivo, forming a positive feedback regulatory loop.
Over-expression of Grhl2 causes spina bifida in the Axial defects mutant mouse
tissue closure defects in Grhl2 mutants are similar to that of AP-2alpha (show TFAP2A Proteins) null mutants and AP-2alpha (show TFAP2A Proteins) has been shown to bind to the promoter of E-cadherin (show CDH1 Proteins)
The data showed that midbrain-hindbrain boundary maintenance and morphogenesis are dissociable events regulated by grhl2b through diverse transcriptional targets.
This work reveals an evolutionarily conserved function of Grhl2 in otic development and provides a fish model for further studying mechanisms of Grhl2-related hearing loss.
The protein encoded by this gene is a transcription factor that can act as a homodimer or as a heterodimer with either GRHL1 or GRHL3. Defects in this gene are a cause of non-syndromic sensorineural deafness autosomal dominant type 28 (DFNA28).
grainyhead-like 2 (Drosophila)
, transcription factor CP2-like 3
, brother of mammalian grainyhead
, grainyhead-like protein 2 homolog
, grainyhead like 2
, grainyhead-like 2
, grainyhead-like 2b protein