Inhibition of the Androgen Receptor Induces a Novel Tumor Promoter, ZBTB46, for Prostate Cancer Metastasis

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2017 Jul 11

PMID 28692046

Citations 22

Authors

W-Y Chen

Y-C Tsai

M K Siu

H-L Yeh

C-L Chen

J J Yin

J Huang

Y-N Liu

Affiliations

Soon will be listed here.

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.

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