SND1 Binds to ERG and Promotes Tumor Growth in Genetic Mouse Models of Prostate Cancer

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Nov 17

PMID 37973913

Authors

Sheng-You Liao

Dmytro Rudoy

Sander B Frank

Luan T Phan

Olga Klezovitch

Julian Kwan

Ilsa Coleman

Michael C Haffner

Dapei Li

Peter S Nelson

Andrew Emili

Valeri Vasioukhin

Affiliations

Soon will be listed here.

Abstract

SND1 and MTDH are known to promote cancer and therapy resistance, but their mechanisms and interactions with other oncogenes remain unclear. Here, we show that oncoprotein ERG interacts with SND1/MTDH complex through SND1's Tudor domain. ERG, an ETS-domain transcription factor, is overexpressed in many prostate cancers. Knocking down SND1 in human prostate epithelial cells, especially those overexpressing ERG, negatively impacts cell proliferation. Transcriptional analysis shows substantial overlap in genes regulated by ERG and SND1. Mechanistically, we show that ERG promotes nuclear localization of SND1/MTDH. Forced nuclear localization of SND1 prominently increases its growth promoting function irrespective of ERG expression. In mice, prostate-specific Snd1 deletion reduces cancer growth and tumor burden in a prostate cancer model (PB-Cre/Pten/ERG mice), Moreover, we find a significant overlap between prostate transcriptional signatures of ERG and SND1. These findings highlight SND1's crucial role in prostate tumorigenesis, suggesting SND1 as a potential therapeutic target in prostate cancer.

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