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Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
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.
Afiliación
  • Mateo F; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Arenas EJ; Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
  • Aguilar H; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Serra-Musach J; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • de Garibay GR; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Boni J; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Maicas M; Centre for Applied Medical Research (CIMA) and Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain.
  • Du S; Department of Radiation Oncology, New York University School of Medicine, New York, NY, USA.
  • Iorio F; European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.
  • Herranz-Ors C; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
  • Islam A; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Prado X; Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, Bangladesh.
  • Llorente A; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Petit A; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Vidal A; Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Català I; Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Soler T; Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Venturas G; Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Rojo-Sebastian A; Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Serra H; Department of Pathology, MD Anderson Cancer Center, Madrid, Spain.
  • Cuadras D; Angiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Blanco I; Statistics Unit, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Lozano J; Hereditary Cancer Programme, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Canals F; Department of Molecular Biology and Biochemistry, Málaga University, and Molecular Oncology Laboratory, Mediterranean Institute for the Advance of Biotechnology and Health Research (IBIMA), University Hospital Virgen de la Victoria, Málaga, Spain.
  • Sieuwerts AM; ProteoRed-Instituto de Salud Carlos III, Proteomic Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona, Spain.
  • de Weerd V; Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
  • Look MP; Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
  • Puertas S; Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
  • García N; Chemoresistance and Predictive Factors Laboratory, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Perkins AS; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Bonifaci N; University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY, USA.
  • Skowron M; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Gómez-Baldó L; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Hernández V; Breast Cancer and Systems Biology Laboratory, Program Against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology (ICO), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet del Llobregat, Barcelona, Spain.
  • Martínez-Aranda A; Biological Clues of the Invasive and Metastatic Phenotype Laboratory, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Martínez-Iniesta M; Biological Clues of the Invasive and Metastatic Phenotype Laboratory, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Serrat X; Chemoresistance and Predictive Factors Laboratory, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Cerón J; Cancer and Human Molecular Genetics, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
  • Brunet J; Cancer and Human Molecular Genetics, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
  • Barretina MP; Hereditary Cancer Programme, ICO, Girona Biomedical Research Institute (IDIBGI), Girona, Spain.
  • Gil M; Department of Medical Oncology, ICO, IDIBGI, Girona, Spain.
  • Falo C; Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Fernández A; Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Morilla I; Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Pernas S; Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Plà MJ; Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Andreu X; Department of Gynecology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
  • Seguí MA; Department of Pathology, Parc Taulí Hospital Consortium, Sabadell, Barcelona, Spain.
  • Ballester R; Medical Oncology Service, Parc Taulí Hospital Consortium, Sabadell, Barcelona, Spain.
  • Castellà E; Department of Radiation Oncology, University Hospital Germans Trias i Pujol, ICO, Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Spain.
Oncogene ; 36(19): 2737-2749, 2017 05 11.
Article en En | MEDLINE | ID: mdl-27991928
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proto-Oncogenes / Neoplasias de la Mama / Proteínas de Unión al ADN / Factor de Transcripción SOX9 / Serina-Treonina Quinasas TOR / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proto-Oncogenes / Neoplasias de la Mama / Proteínas de Unión al ADN / Factor de Transcripción SOX9 / Serina-Treonina Quinasas TOR / Neoplasias Pulmonares Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Female / Humans / Middle aged Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2017 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido