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Title: Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
Authors: Mateo, F
Arenas, E J
Aguilar, H
Serra-Musach, J
de Garibay, G Ruiz
Boni, J
Maicas, M
Du, S
Iorio, F
Herranz-Ors, C
Islam, A
Prado, X
Llorente, A
Petit, A
Vidal, A
Català, I
Soler, T
Venturas, G
Rojo-Sebastian, A
Serra, H
Cuadras, D
Blanco, I
Lozano, J
Canals, F
Sieuwerts, A M
de Weerd, V
Look, M P
Puertas, S
García, N
Perkins, A S
Bonifaci, N
Skowron, M
Gómez-Baldó, L
Hernández, V
Martínez-Aranda, A
Martínez-Iniesta, M
Serrat, X
Cerón, J
Brunet, J
Barretina, M P
Gil, M
Falo, C
Fernández, A
Morilla, I
Pernas, S
Plà, M J
Andreu, X
Seguí, M A
Ballester, R
Castellà, E
Nellist, M
Morales, S
Valls, J
Velasco, A
Matias-Guiu, X
Figueras, A
Sánchez-Mut, J V
Sánchez-Céspedes, M
Cordero, A
Gómez-Miragaya, J
Palomero, L
Gómez, A
Gajewski, T F
Cohen, E E W
Jesiotr, M
Bodnar, L
Quintela-Fandino, M
López-Bigas, N
Valdés-Mas, R
Puente, X S
Viñals, F
Casanovas, O
Graupera, M
Hernández-Losa, J
Ramón Y Cajal, S
García-Alonso, L
Saez-Rodriguez, J
Esteller, M
Sierra, A
Martín-Martín, N
Matheu, A
Carracedo, A
González-Suárez, E
Nanjundan, M
Cortés, J
Lázaro, C
Odero, M D
Martens, J W M
Moreno-Bueno, G
Barcellos-Hoff, M H
Villanueva, A
Gomis, R R
Pujana, M A
metadata.dc.subject.mesh: Adaptor Proteins, Signal Transducing
Breast Neoplasms
Carrier Proteins
Cell Proliferation
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Lung Neoplasms
MCF-7 Cells
MDS1 and EVI1 Complex Locus Protein
Microfilament Proteins
Middle Aged
Neoplasm Metastasis
Regulatory-Associated Protein of mTOR
SOX9 Transcription Factor
Signal Transduction
TOR Serine-Threonine Kinases
Transcription Factors
Xenograft Model Antitumor Assays
Issue Date: 19-Dec-2016
Abstract: 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.
metadata.dc.identifier.doi: 10.1038/onc.2016.427
Appears in Collections:Producción 2020

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