PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer
dc.contributor.author | Zabala Letona, Amaia | |
dc.contributor.author | Arruabarrena Aristorena, Amaia | |
dc.contributor.author | Fernández Ruiz, Sonia | |
dc.contributor.author | Viera, Cristina | |
dc.contributor.author | Carlevaris, Onintza | |
dc.contributor.author | Ercilla Eguiarte, Amaia | |
dc.contributor.author | Mendizabal, Isabel | |
dc.contributor.author | Martín Mateos, Teresa | |
dc.contributor.author | Macchia, Alice | |
dc.contributor.author | Camacho Soguero, Laura | |
dc.contributor.author | Pujana Vaquerizo, Mikel | |
dc.contributor.author | Sánchez Mosquera, Pilar | |
dc.contributor.author | Torrano Moya, Verónica | |
dc.contributor.author | Martín Martín, Natalia | |
dc.contributor.author | Zuñiga García, Patricia | |
dc.contributor.author | Castillo Martín, Mireia | |
dc.contributor.author | Ugalde Olano, Aitziber | |
dc.contributor.author | Loizaga Iriarte, Ana | |
dc.contributor.author | Unda Urzaiz, Jesús Miguel | |
dc.contributor.author | Mato, José M. | |
dc.contributor.author | Berra Ramírez, Miren Edurne | |
dc.contributor.author | Martínez Chantar, María Luz | |
dc.contributor.author | Carracedo Pérez, Arkaitz | |
dc.date.accessioned | 2022-03-03T08:37:07Z | |
dc.date.available | 2022-03-03T08:37:07Z | |
dc.date.issued | 2022-02 | |
dc.identifier.citation | Oncogenesis 11(1) : (2022) // Article ID 10 | es_ES |
dc.identifier.issn | 2157-9024 | |
dc.identifier.uri | http://hdl.handle.net/10810/55649 | |
dc.description.abstract | [EN] 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. | es_ES |
dc.description.sponsorship | We are grateful to the Carracedo lab for valuable input, to Drs. Ana M. Aransay, James D. Sutherland and F. Elortza for technical advice, and Drs. Michelle Clasquin, Katie Sellers and Katya Marjon at Agios Pharmaceuticals for performing, processing and analyzing the metabolomics experiments. We thank the Basque Biobank for Research (BIOEF) for the support with prostate specimen acquisition and management. A.A-A. was funded by the Basque Government (predoctoral fellowship). V.T. is funded by Fundación Vasca de Innovación e Investigación Sanitarias, BIOEF (BIO15/CA/052), the AECC J.P. Bizkaia, the Basque Department of Health (2016111109) and the MICINN RTI2018-097267-B-I00. I.M. is supported by Fundación Cris Contra el Cáncer (PR_TPD_2020-19). The work of A. Carracedo is supported by the Basque Department of Industry, Tourism and Trade (Elkartek), the department of education (IKERTALDE IT1106-16) and health (RIS3), the BBVA foundation, the MICINN (SAF2016-79381-R; PID2019-108787RB-I00 (FEDER/EU); Severo Ochoa Excellence Accreditation SEV-2016-0644; Excellence Networks RED2018-102769-T), the AECC (GCTRA18006CARR), Vencer el Cáncer Foundation, La Caixa Foundation (ID 100010434), under the agreement LCF/PR/HR17/ and the European Research Council (Starting Grant 336343, PoC 754627, Consolidator Grant 819242). CIBERONC was co-funded with FEDER funds and funded by ISCIII. We are grateful for the support of Mondravember and Movembergara. A.E. was supported by MCIN/AEI/10.13039/501100011033 and the EU programme NextGenerationEU/PRTR (IJC2020-043583-I). The work of JM Mato was supported by NIH grant R01CA172086 and SAF2017-88041-R. EB is funded by the MICINN (BFU2016-76872-R (FEDER/EU), PID2019-108112RB-I00, and Excellence Networks SAF2017-90794-REDT). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer Nature | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/819242 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/SEV-2016-0644 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-097267-B-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-108112RB-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2019-108787RB-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/IJC2020-043583-I | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.title | PI3K-regulated Glycine N-methyltransferase is required for the development of prostate cancer | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41389-022-00382-x | es_ES |
dc.identifier.doi | 10.1038/s41389-022-00382-x | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoes | Cirugía, radiología y medicina física | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
dc.departamentoeu | Kirurgia,erradiologia eta medikuntza fisikoa | es_ES |
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