Palmitoyl acyltransferase ZDHHC7 inhibits androgen receptor and suppresses prostate cancer.
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
16
01
2023
accepted:
04
05
2023
revised:
02
05
2023
medline:
26
6
2023
pubmed:
18
5
2023
entrez:
17
5
2023
Statut:
ppublish
Résumé
The hormonal transcription factor androgen receptor (AR) is a master regulator of prostate cancer (PCa). Protein palmitoylation, which attaches a palmitate fatty acid to a substrate protein, is mediated by a class of 23 ZDHHC (Zinc-Finger DHHC motif)-family palmitoyltransferases. Although palmitoylation has been shown to modify many proteins and regulate diverse cellular processes, little is known about ZDHHC genes in cancer. Here we examined ZDHHC family gene expression in human tissue panels and identified ZDHHC7 as a PCa-relevant member. RNA-seq analyses of PCa cells with ZDHHC7 de-regulation revealed global alterations in androgen response and cell cycle pathways. Mechanistically, ZDHHC7 inhibits AR gene transcription and therefore reduces AR protein levels and abolishes AR signaling in PCa cells. Accordingly, ZDHHC7 depletion increased the oncogenic properties of PCa cells, whereas restoring ZDHHC7 is sufficient to suppress PCa cell proliferation and invasion in vitro and mitigate xenograft tumor growth in vivo. Lastly, we demonstrated that ZDHHC7 is downregulated in human PCa compared to benign-adjacent tissues, and its loss is associated with worse clinical outcomes. In summary, our study reveals a global role of ZDHHC7 in inhibiting androgen response and suppressing PCa progression and identifies ZDHHC7 loss as a biomarker for aggressive PCa and a target for therapeutic intervention.
Identifiants
pubmed: 37198397
doi: 10.1038/s41388-023-02718-2
pii: 10.1038/s41388-023-02718-2
doi:
Substances chimiques
Acyltransferases
EC 2.3.-
Androgens
0
Receptors, Androgen
0
ZDHHC7 protein, human
EC 2.3.1.-
AR protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2126-2138Subventions
Organisme : U.S. Department of Defense (United States Department of Defense)
ID : PC160759P1
Organisme : Prostate Cancer Foundation (PCF)
ID : 2017CHAL2008
Organisme : U.S. Department of Health & Human Services | NIH | Center for Scientific Review (NIH Center for Scientific Review)
ID : R50CA211271
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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