PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer

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 exhibit...

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Published in:Oncogenesis (New York, NY) NY), 2022-02, Vol.11 (1), p.10-10, Article 10
Main Authors: Zabala-Letona, Amaia, Arruabarrena-Aristorena, Amaia, Fernandez-Ruiz, Sonia, Viera, Cristina, Carlevaris, Onintza, Ercilla, Amaia, Mendizabal, Isabel, Martin, Teresa, Macchia, Alice, Camacho, Laura, Pujana-Vaquerizo, Mikel, Sanchez-Mosquera, Pilar, Torrano, Verónica, Martin-Martin, Natalia, Zuniga-Garcia, Patricia, Castillo-Martin, Mireia, Ugalde-Olano, Aitziber, Loizaga-Iriarte, Ana, Unda, Miguel, Mato, Jose M., Berra, Edurne, Martinez-Chantar, Maria L., Carracedo, Arkaitz
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
631/67/2327
631/67/589/466
96/95
Apoptosis
Cell Biology
Enzymes
Epigenetics
Glycine N-methyltransferase
Human Genetics
Internal Medicine
Invasiveness
Kinases
Medicine
Medicine & Public Health
Methyltransferase
N-Methyltransferase
Oncology
Pancreas
Prostate cancer
Sarcosine
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cited_by cdi_FETCH-LOGICAL-c540t-dd20b9859185ae7f849e3610f531a574732cb9f03deb947ae0ba0f6436cc298f3
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container_title Oncogenesis (New York, NY)
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creator Zabala-Letona, Amaia
Arruabarrena-Aristorena, Amaia
Fernandez-Ruiz, Sonia
Viera, Cristina
Carlevaris, Onintza
Ercilla, Amaia
Mendizabal, Isabel
Martin, Teresa
Macchia, Alice
Camacho, Laura
Pujana-Vaquerizo, Mikel
Sanchez-Mosquera, Pilar
Torrano, Verónica
Martin-Martin, Natalia
Zuniga-Garcia, Patricia
Castillo-Martin, Mireia
Ugalde-Olano, Aitziber
Loizaga-Iriarte, Ana
Unda, Miguel
Mato, Jose M.
Berra, Edurne
Martinez-Chantar, Maria L.
Carracedo, Arkaitz
description 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.
doi_str_mv 10.1038/s41389-022-00382-x
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ispartof Oncogenesis (New York, NY), 2022-02, Vol.11 (1), p.10-10, Article 10
issn 2157-9024
2157-9024
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subjects 1-Phosphatidylinositol 3-kinase
631/67/2327
631/67/589/466
96/95
Apoptosis
Cell Biology
Enzymes
Epigenetics
Glycine N-methyltransferase
Human Genetics
Internal Medicine
Invasiveness
Kinases
Medicine
Medicine & Public Health
Methyltransferase
N-Methyltransferase
Oncology
Pancreas
Prostate cancer
Sarcosine
title PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T18%3A40%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=PI3K-regulated%20Glycine%20N-methyltransferase%20is%20required%20for%20the%20development%20of%20prostate%20cancer&rft.jtitle=Oncogenesis%20(New%20York,%20NY)&rft.au=Zabala-Letona,%20Amaia&rft.date=2022-02-23&rft.volume=11&rft.issue=1&rft.spage=10&rft.epage=10&rft.pages=10-10&rft.artnum=10&rft.issn=2157-9024&rft.eissn=2157-9024&rft_id=info:doi/10.1038/s41389-022-00382-x&rft_dat=%3Cproquest_doaj_%3E2632809772%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c540t-dd20b9859185ae7f849e3610f531a574732cb9f03deb947ae0ba0f6436cc298f3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2632027279&rft_id=info:pmid/35197445&rfr_iscdi=true