PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer.
Journal
Oncogenesis
ISSN: 2157-9024
Titre abrégé: Oncogenesis
Pays: United States
ID NLM: 101580004
Informations de publication
Date de publication:
23 Feb 2022
23 Feb 2022
Historique:
received:
02
03
2021
accepted:
24
01
2022
revised:
23
12
2021
entrez:
24
2
2022
pubmed:
25
2
2022
medline:
25
2
2022
Statut:
epublish
Résumé
Glycine N-Methyltransferase (GNMT) is a metabolic enzyme that integrates metabolism and epigenetic regulation. The product of GNMT, sarcosine, has been proposed as a prostate cancer biomarker. This enzyme is predominantly expressed in the liver, brain, pancreas, and prostate tissue, where it exhibits distinct regulation. Whereas genetic alterations in GNMT have been associated to prostate cancer risk, its causal contribution to the development of this disease is limited to cell line-based studies and correlative human analyses. Here we integrate human studies, genetic mouse modeling, and cellular systems to characterize the regulation and function of GNMT in prostate cancer. We report that this enzyme is repressed upon activation of the oncogenic Phosphoinositide-3-kinase (PI3K) pathway, which adds complexity to its reported dependency on androgen signaling. Importantly, we demonstrate that expression of GNMT is required for the onset of invasive prostate cancer in a genetic mouse model. Altogether, our results provide further support of the heavy oncogenic signal-dependent regulation of GNMT in prostate cancer.
Identifiants
pubmed: 35197445
doi: 10.1038/s41389-022-00382-x
pii: 10.1038/s41389-022-00382-x
pmc: PMC8866399
doi:
Types de publication
Journal Article
Langues
eng
Pagination
10Subventions
Organisme : NCI NIH HHS
ID : R01 CA172086
Pays : United States
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : 819242
Informations de copyright
© 2022. The Author(s).
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