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Citations to this article

Aberrant nuclear localization of EBP50 promotes colorectal carcinogenesis in xenotransplanted mice by modulating TCF-1 and β-catenin interactions
Yu-Yu Lin, … , Chi-Ling Chen, Tzuu-Shuh Jou
Yu-Yu Lin, … , Chi-Ling Chen, Tzuu-Shuh Jou
Published April 2, 2012
Citation Information: J Clin Invest. 2012;122(5):1881-1894. https://doi.org/10.1172/JCI45661.
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Research Article Oncology Article has an altmetric score of 1

Aberrant nuclear localization of EBP50 promotes colorectal carcinogenesis in xenotransplanted mice by modulating TCF-1 and β-catenin interactions

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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.

Authors

Yu-Yu Lin, Yung-Ho Hsu, Hsin-Yi Huang, Yih-Jyh Shann, Chi-Ying F. Huang, Shu-Chen Wei, Chi-Ling Chen, Tzuu-Shuh Jou

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Total citations by year

Year: 2023 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 Total
Citations: 3 2 1 3 2 1 3 1 3 3 1 23
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Citations to this article (23)

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Non-viral gene therapy using RNA interference with PDGFR-α mediated epithelial-mesenchymal transformation for proliferative vitreoretinopathy
Wang J, Zhao P, Chen Z, Wang H, Wang Y, Lin Q
2023
TMIGD1: Emerging functions of a tumor supressor and adhesion receptor.
Thüring EM, Hartmann C, Schwietzer YA, Ebnet K
Oncogene 2023
EBP50 Depletion and Nuclear β-Catenin Accumulation Engender Aggressive Behavior of Colorectal Carcinoma through Induction of Tumor Budding
Itou T, Ishibashi Y, Oguri Y, Hashimura M, Yokoi A, Harada Y, Fukagawa N, Hayashi M, Ono M, Kusano C, Saegusa M
Cancers 2023
MINDIN Exerts Protumorigenic Actions on Primary Prostate Tumors via Downregulation of the Scaffold Protein NHERF-1
L Álvarez-Carrión, I Gutiérrez-Rojas, MR Rodríguez-Ramos, JA Ardura, V Alonso
Cancers 2021
PSPC1 is a new contextual determinant of aberrant subcellular translocation of oncogenes in tumor progression
YD Lang, YS Jou
Journal of Biomedical Science 2021
Automated classification of protein subcellular localization in immunohistochemistry images to reveal biomarkers in colon cancer
ZZ Xue, Y Wu, QZ Gao, L Zhao, YY Xu
BMC bioinformatics 2020
Specificity of NHERF1 regulation of GPCR signaling and function in human airway smooth muscle
T Pera, E Tompkins, M Katz, B Wang, DA Deshpande, EJ Weinman, RB Penn
The FASEB Journal 2019
Nek2B activates the wnt pathway and promotes triple-negative breast cancer chemothezrapy-resistance by stabilizing β-catenin
H Shen, W Yan, J Yuan, Z Wang, C Wang
Journal of Experimental & Clinical Cancer Research 2019
Prognostic and therapeutic implications of NHERF1 expression and regulation in colorectal cancer
PD Leiphrakpam, AJ Lazenby, S Chowdhury, LM Smith, M Mathiesen, MG Brattain, J Wang, JD Black, C Are
Journal of Surgical Oncology 2019
NHERF1 Between Promises and Hopes: Overview on Cancer and Prospective Openings
M Centonze, C Saponaro, A Mangia
Translational oncology 2018
Ezrin–Radixin–Moesin Binding Phosphoprotein 50: A Potential Novel Biomarker in Human Papilloma Virus-Associated Head and Neck Squamous Cell Carcinomas
A Shankar, DH Crouch, M Macluskey
Head and Neck Pathology 2018
Role of the PDZ-scaffold protein NHERF1/EBP50 in cancer biology: from signaling regulation to clinical relevance
J Vaquero, TH Ho-Bouldoires, A Clapéron, L Fouassier
Oncogene 2017
Gankyrin sustains PI3K/GSK-3β/β-catenin signal activation and promotes colorectal cancer aggressiveness and progression
F He, H Chen, P Yang, Q Wu, T Zhang, C Wang, J Wei, Z Chen, H Hu, W Li, J Cao
Oncotarget 2016
β-catenin interaction with NHERF1 and RASSF1A methylation in metastatic colorectal cancer patients
L Schirosi, A Mazzotta, G Opinto, R Pinto, G Graziano, S Tommasi, L Fucci, G Simone, A Mangia
Oncotarget 2016
Ras-activated RSK1 phosphorylates EBP50 to regulate its nuclear localization and promote cell proliferation
Lim H, Jou TS
Oncotarget 2016
NHERF1/EBP50 is an organizer of polarity structures and a diagnostic marker in ependymoma
MM Georgescu, P Yell, BC Mobley, P Shang, T Georgescu, SH Wang, P Canoll, KJ Hatanpaa, CL White, JM Raisanen
Acta Neuropathologica Communications 2015
Protein mislocalization: Mechanisms, functions and clinical applications in cancer
X Wang, S Li
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2014
EBP50 regulates the apoptosis of pancreatic cancer cells by decreasing the expression levels of Bcl-2
M Ji, L Yuan, X Lv, W Dong, X Peng
Experimental and therapeutic medicine 2014
Polarized and Stage-Dependent Distribution of Immunoreactivity for Novel PDZ-Binding Protein Preso1 in Adult Neurogenic Regions
ES Lee, WR Kim, Y Kim, HW Lee, H Kim, W Sun
Endocrinology and Metabolism 2014
Tumor suppressor function of ezrin-radixin-moesin-binding phosphoprotein-50 through β-catenin/E-cadherin pathway in human hepatocellular cancer
XL Peng, MY Ji, ZR Yang, J Song, WG Dong
World journal of gastroenterology : WJG 2013
dCTP pyrophosphohydrase exhibits nucleic accumulation in multiple carcinomas
Y Zhang, WY Ye, JQ Wang, SJ Wang, P Ji, GY Zhou, GP Zhao, HL Ge, Y Wang
European Journal of Histochemistry : EJH 2013
In MMTV-Her-2/neu transgenic mammary tumors the absence of caveolin-1-/- alters PTEN and NHERF1 but not β-catenin expression
FD Cuello-Carrión, N Cayado-Gutiérrez, AL Natoli, C Restall, RL Anderson, S Nadin, D Alvarez-Olmedo, GN Castro, FE Gago, MA Fanelli, DR Ciocca
Cell Stress and Chaperones 2013
Wnt pathway activity confers chemoresistance to cancer stem-like cells in a neuroblastoma cell line
SD Vangipuram, SA Buck, WD Lyman
Tumor Biology 2012

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