Linking β-catenin to androgen-signaling pathway

Fajun Yang, Xiaoyu Li, Manju Sharma, Carl Y. Sasaki, Dan L. Longo, Bing Lim, Zijie Sun

Research output: Contribution to journalArticle

275 Scopus citations

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. β-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 β-catenin and AR. Unlike the steroid hormone receptor coactivator I (SRC1), β-catenin showed a strong interaction with AR but not with other steroid hormone receptors such as estrogen receptor α, progesterone receptor β, and glucocorticoid receptor. The ligand binding domain of AR and the NH2 terminus combined with the first six armadillo repeats of β-catenin were shown to be necessary for the interaction. Through this specific interaction, β-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 β-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 β-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.

Original languageEnglish (US)
Pages (from-to)11336-11344
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number13
DOIs
StatePublished - Mar 29 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Yang, F., Li, X., Sharma, M., Sasaki, C. Y., Longo, D. L., Lim, B., & Sun, Z. (2002). Linking β-catenin to androgen-signaling pathway. Journal of Biological Chemistry, 277(13), 11336-11344. https://doi.org/10.1074/jbc.M111962200