SND1 binds to ERG and promotes tumor growth in genetic mouse models of prostate cancer

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 and Valeri Vasioukhin ()
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Sheng-You Liao: Fred Hutchinson Cancer Center
Dmytro Rudoy: Fred Hutchinson Cancer Center
Sander B. Frank: Fred Hutchinson Cancer Center
Luan T. Phan: Fred Hutchinson Cancer Center
Olga Klezovitch: Fred Hutchinson Cancer Center
Julian Kwan: Boston University
Ilsa Coleman: Fred Hutchinson Cancer Center
Michael C. Haffner: Fred Hutchinson Cancer Center
Dapei Li: University of Washington
Peter S. Nelson: Fred Hutchinson Cancer Center
Andrew Emili: Boston University
Valeri Vasioukhin: Fred Hutchinson Cancer Center

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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/Ptenflox/flox/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.

Date: 2023
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DOI: 10.1038/s41467-023-43245-8

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