https://scholars.lib.ntu.edu.tw/handle/123456789/563145
標題: | Direct interaction of β-catenin with nuclear ESM1 supports stemness of metastatic prostate cancer | 作者: | Pan K.-F. Lee W.-J. Chou C.-C. Yang Y.-C. Chang Y.-C. Chien M.-H. Hsiao M. KUO-TAI HUA |
關鍵字: | cancer stemness; tumor metastasis; Wnt-β-catenin | 公開日期: | 2021 | 出版社: | Wiley-VCH Verlag | 卷: | 40 | 期: | 4 | 來源出版物: | EMBO Journal | 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. ? 2020 The Authors |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85097851509&doi=10.15252%2fembj.2020105450&partnerID=40&md5=4783f16e76f47c25f202adb1d27f0da2 https://scholars.lib.ntu.edu.tw/handle/123456789/563145 |
ISSN: | 0261-4189 | DOI: | 10.15252/embj.2020105450 | SDG/關鍵字: | beta catenin; endothelial cell specific molecule 1; proteoglycan; transcription factor 4; unclassified drug; Wnt protein; beta catenin; CTNNB1 protein, human; ESM1 protein, human; proteoglycan; tumor marker; tumor protein; animal cell; animal experiment; animal model; armadillo repeat domain; Article; cancer stem cell; canonical Wnt signaling; complex formation; controlled study; correlation analysis; human; human cell; male; metastasis; metastatic prostate cancer; mouse; nonhuman; overall survival; prostate cancer; protein expression; protein protein interaction; protein structure; transactivation; tumor invasion; animal; apoptosis; cell nucleus; cell proliferation; drug screening; gene expression regulation; genetics; lung tumor; metabolism; nonobese diabetic mouse; pathology; prognosis; prostate tumor; SCID mouse; tumor cell culture; Animals; Apoptosis; beta Catenin; Biomarkers, Tumor; Cell Nucleus; Cell Proliferation; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Proteins; Neoplastic Stem Cells; Prognosis; Prostatic Neoplasms; Proteoglycans; Tumor Cells, Cultured; Xenograft Model Antitumor Assays |
顯示於: | 毒理學研究所 |
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