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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chen, W-Y; Tsai, Y-C; Siu, MK; Yeh, H-L; Chen, C-L; Yin, JJ; Huang, J; Liu, Y-N

Published Date

  • November 9, 2017

Published In

Volume / Issue

  • 36 / 45

Start / End Page

  • 6213 - 6224

PubMed ID

  • 28692046

Pubmed Central ID

  • 28692046

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

Digital Object Identifier (DOI)

  • 10.1038/onc.2017.226

Language

  • eng

Conference Location

  • England