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Prostate. 2018 Dec;78(16):1311-1320. doi: 10.1002/pros.23704. Epub 2018 Jul 26.

Wnt receptor Frizzled 8 is a target of ERG in prostate cancer.

Author information

1
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
2
Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
3
Vattikuti Urology Institute, Department of Urology, Henry Ford Health System, Detroit, Michigan.
4
Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
5
Department of Urology, University of Alabama at Birmingham, Birmingham, Alabama.

Abstract

Prostate cancer (PCa) is one of the most frequently diagnosed cancers among men. Many molecular changes have been detailed during PCa progression. The gene encoding the transcription factor ERG shows recurrent rearrangement, resulting in the overexpression of ERG in the majority of prostate cancers. Overexpression of ERG plays a critical role in prostate oncogenesis and development of metastatic disease. Among the downstream effectors of ERG, Frizzled family member FZD4 has been shown to be a target of ERG. Frizzled-8 (FZD8) has been shown to be involved in PCa bone metastasis. In the present study, we show that the expression of FZD8 is directly correlated with ERG expression in PCa. Furthermore, we show that ERG directly targets and activates FZD8 by binding to its promoter. This activation is specific to ETS transcription factor ERG and not ETV1. We propose that ERG overexpression in PCa leads to induction of Frizzled family member FZD8, which is known to activate the Wnt pathway. Taken together, these findings uncover a novel mechanism for PCa metastasis, and indicate that FZD8 may represent a potential therapeutic target for PCa.

KEYWORDS:

ERG; Frizzled 8; Wnt signaling; metastasis; prostate cancer

PMID:
30051493
DOI:
10.1002/pros.23704
[Indexed for MEDLINE]

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