Cited by 342Prostate Cancer Treatment and ResearchWnt/β-catenin signaling in development and cancerEstrogen and related hormone effects

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Linking β-Catenin to Androgen-signaling Pathway

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Yang, Fajun, Li, Xiaoyu, Sharma, Manju, Sasaki, Carl Y., Longo, Dan L., Lim, Bing, Sun, Zijie·2002·Journal of Biological Chemistry

DOI 10.1074/jbc.m111962200

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Abstract

The androgen-signaling pathway is important for the growth and progression of prostate cancer cells. The growth-promoting effects of androgen on prostate cells are mediated mostly through the androgen receptor (AR). There is increasing evidence that transcription activation by AR is mediated through interaction with other cofactors. beta-Catenin plays a critical role in embryonic development and tumorigenesis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction. Here, we demonstrate that a specific protein-protein interaction occurs between beta-catenin and AR. Unlike the steroid hormone receptor coactivator 1 (SRC1), beta-catenin showed a strong interaction with AR but not with other steroid hormone receptors such as estrogen receptor alpha, progesterone receptor beta, and glucocorticoid receptor. The ligand binding domain of AR and the NH(2) terminus combined with the first six armadillo repeats of beta-catenin were shown to be necessary for the interaction. Through this specific interaction, beta-catenin augments the ligand-dependent activity of AR in prostate cancer cells. Moreover, expression of E-cadherin in E-cadherin-negative prostate cancer cells results in redistribution of the cytoplasmic beta-catenin to the cell membrane and reduction of AR-mediated transcription. These data suggest that loss of E-cadherin can elevate the cellular levels of beta-catenin in prostate cancer cells, which may directly contribute to invasiveness and a more malignant tumor phenotype by augmenting AR activity during prostate cancer progression.

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Authors: Yang, F., Li, X., Sharma, M., Sasaki, C. Y., Longo, D. L., Lim, B., & Sun, Z.
Affiliations: Stanford Medicine (US)
Beth Israel Deaconess Medical Center (US)
National Institutes of Health (US)
Corresponding author: Sun, Zijie
ORCID: Yang, Fajun
Li, Xiaoyu
Lim, Bing
Sun, Zijie
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2002-03
Volume: 277
Issue: 13
Pages: 11336-11344
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m111962200
OpenAlex: W2022810442
Cited by: 342
References: 54
Citations by year: 2026: 3 · 2025: 4 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 4 · 2020: 10 · 2019: 14 · 2018: 10 · 2017: 19 · 2016: 7 · 2015: 17 · 2014: 12 · 2013: 19 · 2012: 10
FWCI: 20.23
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 6800 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r01dk054417-01)
National Cancer Institute (CA-70297, R01CA087767, R29CA070297, R01CA070297)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK061002, DK54417, R56DK061002, R01DK047636, DK47636)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords: β-catenin, androgen receptor, androgen signaling, prostate cancer, protein-protein interaction, E-cadherin, Wnt signaling, armadillo repeats, transcriptional coactivation, steroid hormone receptors, tumor progression, cell adhesion
MeSH terms: Androgens, Cytoskeletal Proteins, Humans, Ligands, Male, Prostatic Neoplasms, Receptors, Androgen, Tumor Cells, Cultured, Signal Transduction, Trans-Activators, Two-Hybrid System Techniques, beta Catenin

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Linking β-Catenin to Androgen-signaling Pathway

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