dc.contributor.author |
Zabala-Letona, Amaia |
dc.contributor.author |
Arruabarrena-Aristorena, Amaia |
dc.contributor.author |
Martín Martín, Natalia |
dc.contributor.author |
Fernández Ruiz, Sonia |
dc.contributor.author |
Sutherland, James D. |
dc.contributor.author |
Clasquin, Michelle |
dc.contributor.author |
Tomás Cortázar, Julen |
dc.contributor.author |
Jiménez, José |
dc.contributor.author |
Torres Ramírez, Inés Ma. de |
dc.contributor.author |
Quang, Phong |
dc.contributor.author |
Ximénez-Embún, Pilar |
dc.contributor.author |
Bago, Ruzica |
dc.contributor.author |
Ugalde Olano, Aitziber |
dc.contributor.author |
Loizaga Iriarte, Ana |
dc.contributor.author |
Lacasa Viscasillas, Isabel |
dc.contributor.author |
Unda, Miguel |
dc.contributor.author |
Torrano, Verónica |
dc.contributor.author |
Cabrera, Diana |
dc.contributor.author |
van Liempd, Sebastiaan M. |
dc.contributor.author |
Cendon, Ylenia |
dc.contributor.author |
Castro, Elena |
dc.contributor.author |
Murray, Stuart |
dc.contributor.author |
Revandkar, Ajinkya |
dc.contributor.author |
Alimonti, Andrea |
dc.contributor.author |
Zhang, Yinan |
dc.contributor.author |
Barnett, Amelia |
dc.contributor.author |
Lein, Gina |
dc.contributor.author |
Pirman, David |
dc.contributor.author |
Cortazar, Ana Rosa |
dc.contributor.author |
Arreal, Leire |
dc.contributor.author |
Prudkin, Ludmila |
dc.contributor.author |
Astobiza, Ianire |
dc.contributor.author |
Valcárcel Jiménez, Lorea |
dc.contributor.author |
Zúñiga-García, Patricia |
dc.contributor.author |
Fernández Domínguez, Itziar |
dc.contributor.author |
Piva, Marco |
dc.contributor.author |
Caro-Maldonado, Alfredo |
dc.contributor.author |
Sánchez Mosquera, Pilar |
dc.contributor.author |
Castillo Martín, Mireia |
dc.contributor.author |
Serra, Violeta |
dc.contributor.author |
Beraza, Naiara |
dc.contributor.author |
Gentilella, Antonio |
dc.contributor.author |
Thomas, George |
dc.contributor.author |
Azkargorta, Mikel |
dc.contributor.author |
Elortza, Felix |
dc.contributor.author |
Farràs, Rosa |
dc.contributor.author |
Olmos, David |
dc.contributor.author |
Efeyan, Alejo |
dc.contributor.author |
Anguita, Juan |
dc.contributor.author |
Muñoz, Javier |
dc.contributor.author |
Falcón Pérez, Juan M. |
dc.contributor.author |
Barrio, Rosa |
dc.contributor.author |
Macarulla Mercadé, Teresa |
dc.contributor.author |
Mato, José M. |
dc.contributor.author |
Martínez Chantar, Maria L. |
dc.contributor.author |
Cordon Cardo, Carlos |
dc.contributor.author |
Aransay, Ana M. |
dc.contributor.author |
Marks, Kevin |
dc.contributor.author |
Baselga Torres, Josep, |
dc.contributor.author |
Tabernero, Josep |
dc.contributor.author |
Nuciforo, Paolo |
dc.contributor.author |
Manning, Brendan D. |
dc.contributor.author |
Marjon, Katya |
dc.contributor.author |
Carracedo, Arkaitz |
dc.contributor.author |
Universitat Autònoma de Barcelona |
dc.date |
2017 |
dc.identifier |
https://ddd.uab.cat/record/186284 |
dc.identifier |
urn:10.1038/nature22964 |
dc.identifier |
urn:oai:ddd.uab.cat:186284 |
dc.identifier |
urn:pmid:28658205 |
dc.identifier |
urn:pmcid:PMC5505479 |
dc.identifier |
urn:pmc-uid:5505479 |
dc.identifier |
urn:articleid:14764687v547p109 |
dc.identifier |
urn:scopus_id:85022206445 |
dc.identifier |
urn:altmetric_id:21395996 |
dc.identifier |
urn:oai:egreta.uab.cat:publications/9ebe038e-fc38-4f56-9a63-adec981ffee6 |
dc.identifier |
urn:oai:pubmedcentral.nih.gov:5505479 |
dc.format |
application/pdf |
dc.language |
eng |
dc.publisher |
|
dc.relation |
Ministerio de Economía y Competitividad BFU2014-52282-P |
dc.relation |
Ministerio de Economía y Competitividad BFU2011-25986 |
dc.relation |
Ministerio de Economía y Competitividad SAF2016-79381-R |
dc.relation |
Ministerio de Economía y Competitividad SAF2014-54658-R |
dc.relation |
Ministerio de Economía y Competitividad SAF2015-66312 |
dc.relation |
Ministerio de Economía y Competitividad SAF2014-52097-R |
dc.relation |
Ministerio de Economía y Competitividad SAF2015-67538-R |
dc.relation |
Ministerio de Economía y Competitividad SAF2015-65327-R |
dc.relation |
Ministerio de Economía y Competitividad SAF2011-24967 |
dc.relation |
European Commission 336343 |
dc.relation |
European Commission 754627 |
dc.relation |
European Commission 660191 |
dc.relation |
European Commission 602272 |
dc.relation |
European Commission 638891 |
dc.relation |
Instituto de Salud Carlos III PI10/01484 |
dc.relation |
Instituto de Salud Carlos III PI13/00031 |
dc.relation |
Instituto de Salud Carlos III PT13/0001 |
dc.relation |
Instituto de Salud Carlos III PI15/209 |
dc.relation |
Instituto de Salud Carlos III PI13/01714 |
dc.relation |
Instituto de Salud Carlos III CP14/00228 |
dc.relation |
Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1331 |
dc.relation |
Nature ; Vol. 547 (July 2017), p. 109-113 |
dc.rights |
open access |
dc.rights |
Tots els drets reservats. |
dc.rights |
https://rightsstatements.org/vocab/InC/1.0/ |
dc.title |
mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer |
dc.type |
Article |
dc.description.abstract |
Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
dc.description.abstract |
Activation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation,. Here we show that mTORC1 regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. Through the use of integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identified alterations in tumours impacting on the production of decarboxylated S-adenosylmethionine (dcSAM) and polyamine synthesis. Mechanistically, this metabolic rewiring stems from mTORC1-dependent regulation of S-adenosylmethionine decarboxylase 1 (AMD1) stability. This novel molecular regulation was validated in murine and human cancer specimens. AMD1 was upregulated in prostate cancer specimens with activated mTORC1. Conversely, samples from a clinical trial with the mTORC1 inhibitor everolimus exhibited a predominant decrease in AMD1 immunoreactivity that was associated to a decrease in proliferation, in line with the requirement of dcSAM production for oncogenicity. These findings provide fundamental information about the complex regulatory landscape controlled by mTORC1 to integrate and translate growth signals into an oncogenic metabolic program. |