ArticleOncogene2015
ZEB1 and TCF4 reciprocally modulate their transcriptional activities to regulate Wnt target gene expression.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Pooled it
- Implication of Epigenetic Alterations of ZEB1 in Colorectal Cancer (CRC) Pathogenesis and Therapy Development.Current issues in molecular biology · 2026Review
- Epithelial-mesenchymal dynamics in cancer: Role of signalling pathways, stromal interactions and natural therapies.ADMET & DMPK · 2025Review
- Transcriptomic analysis implicates the involvement of RBM20 in Fuchs' endothelial corneal dystrophy with TCF4 repeat expansion.PloS one · 2025Article
- The decrease in zinc-finger E-box-binding homeobox-1 could accelerate steroid-induced osteonecrosis of the femoral head by repressing type-H vessel formation via Wnt/β-catenin pathway.Animal models and experimental medicine · 2024Article
- Transcription factor interactions explain the context-dependent activity of CRX binding sites.PLoS computational biology · 2024Article
- Article
- ZEB1 promotes non-homologous end joining double-strand break repair.Nucleic acids research · 2023Article
- Wingless/It/β-catenin signaling in liver metastasis from colorectal cancer: A focus on biological mechanisms and therapeutic opportunities.World journal of gastroenterology · 2023Review
- ZEB1 is a Subgroup-Specific Marker of Prognosis and Potential Drug Target in Medulloblastoma.Neuromolecular medicine · 2023Article
- Tumour-associated macrophages enhance breast cancer malignancy via inducing ZEB1-mediated DNMT1 transcriptional activation.Cell & bioscience · 2022Article
- Transcriptional and post-transcriptional control of epithelial-mesenchymal plasticity: why so many regulators?Cellular and molecular life sciences : CMLS · 2022Review
- The Role of MacroH2A Histone Variants in Cancer.Cancers · 2021Review
- Accurate prediction ofNAR genomics and bioinformatics · 2021Article
- Article
- Genome-wide cooperation of EMT transcription factor ZEB1 with YAP and AP-1 in breast cancer.The EMBO journal · 2020Article
- Molecular Mechanisms of Fuchs and Congenital Hereditary Endothelial Corneal Dystrophies.Reviews of physiology, biochemistry and pharmacology · 2020Review
- Genetic Ancestry-dependent Differences in Breast Cancer-induced Field Defects in the Tumor-adjacent Normal Breast.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- ZEB1 protects skeletal muscle from damage and is required for its regeneration.Nature communications · 2019Article
- TBL1 is required for the mesenchymal phenotype of transformed breast cancer cells.Cell death & disease · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The canonical Wnt pathway (TCF4/β-catenin) has important roles during normal differentiation and in disease. Some Wnt functions depend on signaling gradients requiring the pathway to be tightly regulated. A key Wnt target is the transcription factor ZEB1 whose expression by cancer cells promotes tumor invasiveness by repressing the expression of epithelial specification markers and activating mesenchymal genes, including a number of Wnt targets such as LAMC2 and uPA. The ability of ZEB1 to activate/repress its target genes depends on its recruitment of corepressors (CtBP, BRG1) or coactivators (p300) although conditions under which ZEB1 binds these cofactors are not elucidated. Here, we show that TCF4 and ZEB1 reciprocally modulate each other's transcriptional activity: ZEB1 enhances TCF4/β-catenin-mediated transcription and, in turn, Wnt signaling switches ZEB1 from a repressor into an activator. In colorectal cancer (CRC) cells with active Wnt signaling, ZEB1 enhances transcriptional activation of LAMC2 and uPA by TCF4/β-catenin. However, in CRC cells with inactive Wnt, ZEB1 represses both genes. Reciprocal modulation of ZEB1 and TCF4 activities involves their binding to DNA and mutual interaction. Wnt signaling turns ZEB1 into an activator by replacing binding of CtBP/BRG1 in favor of p300. Using a mouse model of Wnt-induced intestinal tumorigenesis, we found that downregulation of ZEB1 reduces the expression of LAMC2 in vivo. These results identify a mechanism through which Wnt and ZEB1 transcriptional activities are modulated, offering new approaches in cancer therapy.
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Registered trials
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.