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

W. Y. Chen, Y. C. Tsai, M. K. Siu, H. L. Yeh, C. L. Chen, J. J. Yin, J. Huang, Y. N. Liu

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)6213-6224
Number of pages12
JournalOncogene
Volume36
Issue number45
DOIs
Publication statusPublished - Nov 9 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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