Ask about this productRelated genes to: TCF8 antibody
- Gene:
- ZEB1 NIH gene
- Name:
- zinc finger E-box binding homeobox 1
- Previous symbol:
- TCF8, PPCD3
- Synonyms:
- BZP, ZEB, AREB6, NIL-2-A, Zfhep, Zfhx1a, FECD6
- Chromosome:
- 10p11.22
- Locus Type:
- gene with protein product
- Date approved:
- 1991-12-17
- Date modifiied:
- 2014-11-19
Related products to: TCF8 antibody
Related articles to: TCF8 antibody
- Acquired resistance to osimertinib remains a major barrier in EGFR-mutant lung adenocarcinoma (LUAD), and in many patients cannot be explained by secondary targetable mutations. This pattern highlights a central role for non-genetic plasticity programs, including epithelial-mesenchymal transition (EMT), drug tolerance, immune evasion, and lineage switch. Here, we used a systems-level framework to define how these processes are coordinated. We constructed a minimal gene regulatory network integrating core EMT regulators with AXL, RB1, PD-L1, and NF-κB, and analysed its emergent behaviour using dynamical simulations. The network resolved into two mutually inhibitory, self-reinforcing "teams": an epithelial/sensitive team centred on RB1, miR-200, miR-34, p53, and E-cadherin, and a mesenchymal/resistant team centred on ZEB1, SNAIL, AXL, PD-L1, and NF-κB. Simulations predicted a strong coupling between EMT and osimertinib resistance, which was validated across bulk transcriptomic datasets from NSCLC cell lines, EGFR-mutant patient cohorts, and perturbation experiments. Inducing EMT increased RB1-loss programs, whereas osimertinib exposure induced AXL and EMT programs, supporting bidirectional regulation and reinforcement. Single-cell and spatial transcriptomic analyses further showed that EMT, AXL, PD-L1 activity, and reduced RB1 signaling co-occur within tumors. Clinically, activation of individual axes such as EMT, RB1 loss, or PD-L1 upregulation was associated with worse outcomes, while combined activation produced markedly poorer survival than any single axis alone. Extending the network to incorporate lineage regulators further linked a partial LUAD-to-LUSC shift with EMT, RB1 loss, and resistance. Together, these findings identify a network topology that coordinates multiple plasticity programs driving osimertinib resistance and suggest that disrupting this cooperative architecture may offer a therapeutic strategy in EGFR-mutant LUAD. - Source: PubMed
Publication date: 2026/04/24
Vashista ShreyaMeena Ritesh KumarKulkarni PrakashSalgia RaviThomas AnishJolly Mohit Kumar - Alcohol use disorder (AUD) is a complex polygenic disease. Rodent models of alcohol dependence have been instrumental in modeling various aspects of dependence. Single-nucleus transcriptomics has enabled the profiling of cell-type-specific changes in gene expression in both human AUD and animal models. In this study, we identified shared dysregulated transcriptomic networks (TN), comprising gene co-expression modules and gene regulatory networks (GRNs) in a mouse model of alcohol dependence and individuals with AUD. Through cell-type-specific TN analysis, we identified translationally relevant, conserved dependence dysregulated molecular signatures. We identified conserved dependence-upregulated gene co-expression modules in astrocytes and oligodendrocytes, with hub genes Slc1a3 and Pde4b, respectively. These genes are linked to alcohol dependence mechanisms, such as glutamate signaling, a well-established target of alcohol's effects, and PDE4, whose inhibition has been shown to reduce alcohol intake in preclinical and clinical studies. We then integrated publicly available human and mouse GRN data to identify upstream regulators of alcohol-dysregulated gene signatures in each cell type. This approach revealed a set of transcription factors (TFs), including Mef2a, Mef2c, Jund, Nr3c1, and Zeb1, that were upstream of most dysregulated genes in both the mouse and human datasets and have established relevance to addiction biology, representing promising targets for translational research. Collectively, these findings demonstrate the utility of cross-species, cell-type-specific network analysis for uncovering conserved molecular mechanisms in alcohol dependence. The identification of shared dysregulated networks, cell type homology, and upstream regulators provides a foundation for developing translationally relevant targeting strategies that can be tested in animal models. - Source: PubMed
Publication date: 2026/04/21
Salem NihalWarden AnnaRoberts AmandaRoberto MarisaMayfield R Dayne - Ovarian cancer (OC) remains one of the deadliest gynecological malignancies, largely due to late diagnosis and the emergence of resistance to platinum-based chemotherapy. Long non-coding RNAs (lncRNAs) have recently emerged as key regulators of tumor progression and therapeutic adaptation. In this study, we performed integrative transcriptomic profiling of patient-derived TCGA ovarian tumor samples and carboplatin-resistant A2780 (CBDCA-R-A2780) cells to identify lncRNAs whose dysregulation overlaps between a cell-line resistance model and patient tumors. Our analyses revealed extensive transcriptional remodeling across both datasets, with - consistently emerging as a strongly deregulated transcript. Differential expression analysis showed robust upregulation of - in resistant cells and tumor tissues, accompanied by correlations with epithelial-mesenchymal transition (EMT)-related transcription factors such as and and inverse associations with epithelial markers including . Computational predictions using RIblast identified specific - binding regions with candidate miRNAs and mRNAs, prioritizing EMT-related transcripts (e.g., , , ) with favorable hybridization energies for future validation. Additional prioritized interactors included genes linked to stress response (, ) and invasion (, ). Because A2780 has been discussed as an endometrioid-like/non-serous ovarian cancer model, mechanistic inferences primarily apply to this in vitro context, while TCGA analyses provide associative support rather than mechanistic validation. Collectively, these findings highlight - as a candidate regulator associated with transcriptional reprogramming in OC and a promising prognostic biomarker warranting further functional testing. - Source: PubMed
Publication date: 2026/04/11
Gutierrez AlvaroLarronde CarolinaSilva SaloméCastro ConstanzaMaldonado RodrigoLeón DanielaMachuca JuanIli Carmen GloriaBrebi PriscillaBuchegger KurtViscarra Tamara - Endothelial-to-mesenchymal transition (EndMT) is a phenotypic switch in which endothelial cells acquire mesenchymal characteristics, involving both functional and morphological changes. While EndMT is essential for cardiac development, its aberrant activation contributes to adult cardiovascular pathologies, including calcific aortic valve disease (CAVD). Dysregulation of ectonucleotidases-membrane-bound enzymes that regulate extracellular ATP and adenosine metabolism-has been implicated in such diseases. Altered extracellular nucleotide signaling influences valvular interstitial cell (VIC) degeneration and may interact with valvular endothelial cells (VECs) undergoing EndMT. The objective of this study was to investigate the role of the purinergic signaling system in regulating EndMT in human aortic VECs. Primary human VECs were cultured in vitro and treated with inhibitors of ectonucleoside triphosphate diphosphohydrolase 1 (CD39), ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and 5'-nucleotidase (CD73), alongside adenosine and P2 purinergic receptor agonists. EndMT markers and signaling pathways were assessed via phosphorylation assays and mRNA expression analysis of key transcription factors, including SLUG, SNAIL, ZEB1, and ZEB2. Inhibition of ATP- and AMP-hydrolyzing enzymes (CD39, ENPP1, CD73) enhanced p38 phosphorylation and modulated SLUG expression. Activation of P2 and adenosine A2B receptors altered SNAIL levels, while A2A receptor signaling influenced ZEB1 and ZEB2 expression. These perturbations resulted in pronounced morphological changes consistent with EndMT. In conclusion, dysregulation of the purinergic signaling system induces EndMT in human aortic VECs, highlighting a potential mechanistic link between extracellular nucleotide metabolism and valvular pathology. Targeting purinergic pathways may represent a therapeutic avenue for CAVD and related vascular disorders. - Source: PubMed
Publication date: 2026/04/18
Schmidt VeraWeber AndreasLichtenberg ArturSchrader JürgenMartsch PascalBarth MareikeAkhyari Payam - Gallbladder cancer (GBC) is the most common and aggressive type of tumor occurring in the biliary system. Several studies have indicated the possible functions of circular RNAs (circRNAs) in GBC tumorigenesis. This research aimed to explore the roles of a novel circRNA, circ-ZEB1 (hsa_circ_0093509), in GBC. The expressions of circ-ZEB1, miR-144-3p, and ZEB2 in GBC cells were detected using RT-qPCR or western blot. The subcellular localization of circ-ZEB1 in GBC cells was determined. The function of circ-ZEB1, miR-144-3p, and ZEB2 in GBC cells was assessed by using CCK-8, EdU staining, colony formation, or Transwell assays. The relationship among miR-144-3p and corresponding targets, circ-ZEB1 and ZEB2, was confirmed. Additionally, xenograft experiments were conducted to assess the role of circ-ZEB1 in tumor growth in vivo. circ-ZEB1 was predominantly found in the cytoplasmic region of GBC cells and was upregulated in the GBC cell lines. Suppression of circ-ZEB1 reduced the proliferation and migration of GBC-SD and SGC-996 cells. Knockdown of circ-ZEB1 attenuates tumor growth in vivo. Mechanistically, circ-ZEB1 sponged miR-144-3p, which targeted ZEB2. Additionally, inhibition of miR-144-3p rescues the effects of circ-ZEB1 or ZEB2 knockdown. These results clarified a vital role of the circ-ZEB1/miR-144-3p/ZEB2 axis in GBC advancement, and may serve as a novel therapeutic target for GBC treatment. - Source: PubMed
Huang LuoshunZhang YangYang FanLing YishengZhou Xianfei