2026-04-29T04:08:32Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/251942025-12-18T13:00:37Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Mateo, F author Arenas, E J author Aguilar, H author Serra-Musach, J author de Garibay, G Ruiz author Boni, J author Maicas, M author Du, S author Iorio, F author Herranz-Ors, C author Islam, A author Prado, X author Llorente, A author Petit, A author Vidal, A author Català, I author Soler, T author Venturas, G author Rojo-Sebastian, A author Serra, H author Cuadras, D author Blanco, I author Lozano, J author Canals, F author Sieuwerts, A M author de Weerd, V author Look, M P author Puertas, S author García, N author Perkins, A S author Bonifaci, N author Skowron, M author Gómez-Baldó, L author Hernández, V author Martínez-Aranda, A author Martínez-Iniesta, M author Serrat, X author Cerón, J author Brunet, J author Barretina, M P author Gil, M author Falo, C author Fernández, A author Morilla, I author Pernas, S author Plà, M J author Andreu, X author Seguí, M A author Ballester, R author Castellà, E author Nellist, M author Morales, S author Valls, J author Velasco, A author Matias-Guiu, X author Figueras, A author Sánchez-Mut, J V author Sánchez-Céspedes, M author Cordero, A author Gómez-Miragaya, J author Palomero, L author Gómez, A author Gajewski, T F author Cohen, E E W author Jesiotr, M author Bodnar, L author Quintela-Fandino, M author López-Bigas, N author Valdés-Mas, R author Puente, X S author Viñals, F author Casanovas, O author Graupera, M author Hernández-Losa, J author Ramón Y Cajal, S author García-Alonso, L author Saez-Rodriguez, J author Esteller, M author Sierra, A author Martín-Martín, N author Matheu, A author Carracedo, A author González-Suárez, E author Nanjundan, M author Cortés, J author Lázaro, C author Odero, M D author Martens, J W M author Moreno-Bueno, G author Barcellos-Hoff, M H author Villanueva, A author Gomis, R R author Pujana, M A author 2017-05-11 Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure. https://hdl.handle.net/20.500.12105/25194 27991928 https://pmc.ncbi.nlm.nih.gov/articles/PMC5442428/ BREAST-CANCER MAMMARY STEM MESENCHYMAL TRANSITION EMBRYONIC STEM SELF-RENEWAL EXPRESSION GENES PATHWAY TARGET MOUSE Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.