ArticleThe Journal of clinical investigation2012
Aberrant nuclear localization of EBP50 promotes colorectal carcinogenesis in xenotransplanted mice by modulating TCF-1 and β-catenin interactions.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Non-viral gene therapy using RNA interference with PDGFR-α mediated epithelial-mesenchymal transformation for proliferative vitreoretinopathy.Materials today. Bio · 2023Article
- Review
- PSPC1 is a new contextual determinant of aberrant subcellular translocation of oncogenes in tumor progression.Journal of biomedical science · 2021Review
- MINDIN Exerts Protumorigenic Actions on Primary Prostate Tumors via Downregulation of the Scaffold Protein NHERF-1.Cancers · 2021Article
- Automated classification of protein subcellular localization in immunohistochemistry images to reveal biomarkers in colon cancer.BMC bioinformatics · 2020Article
- Prognostic and therapeutic implications of NHERF1 expression and regulation in colorectal cancer.Journal of surgical oncology · 2020Article
- Specificity of NHERF1 regulation of GPCR signaling and function in human airway smooth muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Nek2B activates the wnt pathway and promotes triple-negative breast cancer chemothezrapy-resistance by stabilizing β-catenin.Journal of experimental & clinical cancer research : CR · 2019Article
- Ezrin-Radixin-Moesin Binding Phosphoprotein 50: A Potential Novel Biomarker in Human Papilloma Virus-Associated Head and Neck Squamous Cell Carcinomas.Head and neck pathology · 2019Article
- NHERF1 Between Promises and Hopes: Overview on Cancer and Prospective Openings.Translational oncology · 2018Review
- Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: from signaling regulation to clinical relevance.Oncogene · 2017Review
- Gankyrin sustains PI3K/GSK-3β/β-catenin signal activation and promotes colorectal cancer aggressiveness and progression.Oncotarget · 2016Article
- β-catenin interaction with NHERF1 and RASSF1A methylation in metastatic colorectal cancer patients.Oncotarget · 2016Article
- Ras-activated RSK1 phosphorylates EBP50 to regulate its nuclear localization and promote cell proliferation.Oncotarget · 2016Article
- NHERF1/EBP50 is an organizer of polarity structures and a diagnostic marker in ependymoma.Acta neuropathologica communications · 2015Article
- EBP50 regulates the apoptosis of pancreatic cancer cells by decreasing the expression levels of Bcl-2.Experimental and therapeutic medicine · 2014Article
- Polarized and Stage-Dependent Distribution of Immunoreactivity for Novel PDZ-Binding Protein Preso1 in Adult Neurogenic Regions.Endocrinology and metabolism (Seoul, Korea) · 2014Article
- Protein mislocalization: mechanisms, functions and clinical applications in cancer.Biochimica et biophysica acta · 2014Review
- dCTP pyrophosphohydrase exhibits nucleic accumulation in multiple carcinomas.European journal of histochemistry : EJH · 2013Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of canonical Wnt signaling is thought to play a role in colon carcinogenesis. β-Catenin, a key mediator of the pathway, is stabilized upon Wnt activation and accumulates in the nucleus, where it can interact with the transcription factor T cell factor (TCF) to transactivate gene expression. Normal colonic epithelia express a truncated TCF-1 form, called dnTCF-1, that lacks the critical β-catenin-binding domain and behaves as a transcriptional suppressor. How the cell maintains a balance between the two forms of TCF-1 is unclear. Here, we show that ERM-binding phosphoprotein 50 (EBP50) modulates the interaction between β-catenin and TCF-1. We observed EBP50 localization to the nucleus of human colorectal carcinoma cell lines at low cell culture densities and human primary colorectal tumors that manifested a poor clinical outcome. In contrast, EBP50 was primarily membranous in confluent cell lines. Aberrantly located EBP50 stabilized conventional β-catenin/TCF-1 complexes and connected β-catenin to dnTCF-1 to form a ternary molecular complex that enhanced Wnt/β-catenin signaling events, including the transcription of downstream oncogenes such as c-Myc and cyclin D1. Genome-wide analysis of the EBP50 occupancy pattern revealed consensus binding motifs bearing similarity to Wnt-responsive element. Conventional chromatin immunoprecipitation assays confirmed that EBP50 bound to genomic regions highly enriched with TCF/LEF binding motifs. Knockdown of EBP50 in human colorectal carcinoma cell lines compromised cell cycle progression, anchorage-independent growth, and tumorigenesis in nude mice. We therefore suggest that nuclear EBP50 facilitates colon tumorigenesis by modulating the interaction between β-catenin and TCF-1.
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