Direct interaction of β-catenin with nuclear ESM1 supports stemness of metastatic prostate cancer

Ke Fan Pan, Wei Jiunn Lee, Chun Chi Chou, Yi Chieh Yang, Yu Chan Chang, Ming Hsien Chien, Michael Hsiao, Kuo Tai Hua

研究成果: 雜誌貢獻文章同行評審

2 引文 斯高帕斯(Scopus)

摘要

Wnt/β-catenin signaling is frequently activated in advanced prostate cancer and contributes to therapy resistance and metastasis. However, activating mutations in the Wnt/β-catenin pathway are not common in prostate cancer, suggesting alternative regulations may exist. Here, we report that the expression of endothelial cell-specific molecule 1 (ESM1), a secretory proteoglycan, is positively associated with prostate cancer stemness and progression by promoting Wnt/β-catenin signaling. Elevated ESM1 expression correlates with poor overall survival and metastasis. Accumulation of nuclear ESM1, instead of cytosolic or secretory ESM1, supports prostate cancer stemness by interacting with the ARM domain of β-catenin to stabilize β-catenin–TCF4 complex and facilitate the transactivation of Wnt/β-catenin signaling targets. Accordingly, activated β-catenin in turn mediates the nuclear entry of ESM1. Our results establish the significance of mislocalized ESM1 in driving metastasis in prostate cancer by coordinating the Wnt/β-catenin pathway, with implications for its potential use as a diagnostic or prognostic biomarker and as a candidate therapeutic target in prostate cancer.
原文英語
文章編號e105450
期刊EMBO Journal
40
發行號4
DOIs
出版狀態已發佈 - 二月 15 2021

ASJC Scopus subject areas

  • 神經科學 (全部)
  • 分子生物學
  • 生物化學、遺傳與分子生物學 (全部)
  • 免疫學與微生物學 (全部)

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