RT Journal Article
T1 mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer.
A1 Zabala-Letona, Amaia
A1 Arruabarrena-Aristorena, Amaia
A1 Martín-Martín, Natalia
A1 Fernandez-Ruiz, Sonia
A1 Sutherland, James D
A1 Clasquin, Michelle
A1 Tomas-Cortazar, Julen
A1 Jimenez, Jose
A1 Torres, Ines
A1 Quang, Phong
A1 Ximenez-Embun, Pilar
A1 Bago, Ruzica
A1 Ugalde-Olano, Aitziber
A1 Loizaga-Iriarte, Ana
A1 Lacasa-Viscasillas, Isabel
A1 Unda, Miguel
A1 Torrano, Verónica
A1 Cabrera, Diana
A1 van Liempd, Sebastiaan M
A1 Cendon, Ylenia
A1 Castro, Elena
A1 Murray, Stuart
A1 Revandkar, Ajinkya
A1 Alimonti, Andrea
A1 Zhang, Yinan
A1 Barnett, Amelia
A1 Lein, Gina
A1 Pirman, David
A1 Cortazar, Ana R
A1 Arreal, Leire
A1 Prudkin, Ludmila
A1 Astobiza, Ianire
A1 Valcarcel-Jimenez, Lorea
A1 Zuñiga-García, Patricia
A1 Fernandez-Dominguez, Itziar
A1 Piva, Marco
A1 Caro-Maldonado, Alfredo
A1 Sánchez-Mosquera, Pilar
A1 Castillo-Martín, Mireia
A1 Serra, Violeta
A1 Beraza, Naiara
A1 Gentilella, Antonio
A1 Thomas, George
A1 Azkargorta, Mikel
A1 Elortza, Felix
A1 Farràs, Rosa
A1 Olmos, David
A1 Efeyan, Alejo
A1 Anguita, Juan
A1 Muñoz, Javier
A1 Falcón-Pérez, Juan M
A1 Barrio, Rosa
A1 Macarulla, Teresa
A1 Mato, Jose M
A1 Martinez-Chantar, Maria L
A1 Cordon-Cardo, Carlos
A1 Aransay, Ana M
A1 Marks, Kevin
A1 Baselga, José
A1 Tabernero, Josep
A1 Nuciforo, Paolo
A1 Manning, Brendan D
A1 Marjon, Katya
A1 Carracedo, Arkaitz
AB Activation of the PTEN-PI3K-mTORC1 pathway consolidates metabolic programs that sustain cancer cell growth and proliferation. Here we show that mechanistic target of rapamycin complex 1 (mTORC1) regulates polyamine dynamics, a metabolic route that is essential for oncogenicity. By using integrative metabolomics in a mouse model and human biopsies of prostate cancer, we identify alterations in tumours affecting 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 is validated in mouse and human cancer specimens. AMD1 is upregulated in human prostate cancer with activated mTORC1. Conversely, samples from a clinical trial with the mTORC1 inhibitor everolimus exhibit a predominant decrease in AMD1 immunoreactivity that is associated with 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.
YR 2017
FD 2017-06-28
LK http://hdl.handle.net/10668/11354
UL http://hdl.handle.net/10668/11354
LA en
DS RISalud
RD Apr 11, 2025