Inhibition of the androgen receptor induces a novel tumor promoter, ZBTB46, for prostate cancer metastasis

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17 引文 斯高帕斯(Scopus)

摘要

Current therapeutic regimens for prostate cancer focus on targeting androgen receptor (AR) signaling. However, the AR is a key factor in luminal epithelium differentiation and was shown to have a role as a tumor suppressor. Thus, its inhibition may activate oncogenic pathways that contribute to metastatic castration-resistant prostate cancer (CRPC). Herein, we report a novel tumor promoter, ZBTB46, which is negatively regulated by AR signaling via microRNA (miR)-1-mediated downregulation. ZBTB46 is associated with malignant prostate cancer and is essential for metastasis. Its overexpression can overcome the antitumor effects of miR-1 and promote androgen-independent proliferation. We demonstrated that ZBTB46 can transcriptionally regulate SNAI1, a key epithelial-to-mesenchymal transition (EMT) driver, which could contribute to induction of the EMT after androgen-deprivation therapy and metastasis. Our findings are supportive of the model that disruption of AR's function may predispose prostate cancer to progress to metastatic CRPC.

原文英語
頁(從 - 到)6213-6224
頁數12
期刊Oncogene
36
發行號45
DOIs
出版狀態已發佈 - 十一月 9 2017

ASJC Scopus subject areas

  • 分子生物學
  • 遺傳學
  • 癌症研究

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