Inhibition of the androgen receptor induces a novel tumor promoter, ZBTB46, for prostate cancer metastasis.
Oncogene
; 36(45): 6213-6224, 2017 11 09.
Article
in En
| MEDLINE
| ID: mdl-28692046
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
Receptors, Androgen
/
Prostatic Neoplasms, Castration-Resistant
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Oncogene
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2017
Document type:
Article
Affiliation country:
Taiwan