TY - JOUR
T1 - SND1 binds to ERG and promotes tumor growth in genetic mouse models of prostate cancer
AU - Liao, Sheng You
AU - Rudoy, Dmytro
AU - Frank, Sander B.
AU - Phan, Luan T.
AU - Klezovitch, Olga
AU - Kwan, Julian
AU - Coleman, Ilsa
AU - Haffner, Michael C.
AU - Li, Dapei
AU - Nelson, Peter S.
AU - Emili, Andrew
AU - Vasioukhin, Valeri
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-023-43245-8
DO - 10.1038/s41467-023-43245-8
M3 - Article
C2 - 37973913
AN - SCOPUS:85176942137
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 7435
ER -