title: Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
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.
authors.affiliation: 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.
authors.forename: F
authors.initials: F
authors.lastname: Mateo
authors.affiliation: Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: E J
authors.initials: EJ
authors.lastname: Arenas
authors.affiliation: 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.
authors.forename: H
authors.initials: H
authors.lastname: Aguilar
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Serra-Musach
authors.affiliation: 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.
authors.forename: G Ruiz
authors.initials: GR
authors.lastname: de Garibay
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Boni
authors.affiliation: Centre for Applied Medical Research (CIMA) and Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Maicas
authors.affiliation: Department of Radiation Oncology, New York University School of Medicine, New York, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Du
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.|Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: F
authors.initials: F
authors.lastname: Iorio
authors.affiliation: 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.
authors.forename: C
authors.initials: C
authors.lastname: Herranz-Ors
authors.affiliation: Department of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, Bangladesh.
authors.forename: A
authors.initials: A
authors.lastname: Islam
authors.affiliation: 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.
authors.forename: X
authors.initials: X
authors.lastname: Prado
authors.affiliation: 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.
authors.forename: A
authors.initials: A
authors.lastname: Llorente
authors.affiliation: Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Petit
authors.affiliation: Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Català
authors.affiliation: Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Soler
authors.affiliation: Department of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Venturas
authors.affiliation: Department of Pathology, MD Anderson Cancer Center, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Rojo-Sebastian
authors.affiliation: Angiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: H
authors.initials: H
authors.lastname: Serra
authors.affiliation: Statistics Unit, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Cuadras
authors.affiliation: Hereditary Cancer Programme, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Blanco
authors.affiliation: 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.
authors.forename: J
authors.initials: J
authors.lastname: Lozano
authors.affiliation: ProteoRed-Instituto de Salud Carlos III, Proteomic Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Canals
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Sieuwerts
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
authors.forename: V
authors.initials: V
authors.lastname: de Weerd
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
authors.forename: M P
authors.initials: MP
authors.lastname: Look
authors.affiliation: Chemoresistance and Predictive Factors Laboratory, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Puertas
authors.affiliation: 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.
authors.forename: N
authors.initials: N
authors.lastname: García
authors.affiliation: University of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Perkins
authors.affiliation: 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.
authors.forename: N
authors.initials: N
authors.lastname: Bonifaci
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Skowron
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Gómez-Baldó
authors.affiliation: Biological Clues of the Invasive and Metastatic Phenotype Laboratory, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: V
authors.initials: V
authors.lastname: Hernández
authors.affiliation: Biological Clues of the Invasive and Metastatic Phenotype Laboratory, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Martínez-Aranda
authors.affiliation: Chemoresistance and Predictive Factors Laboratory, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Martínez-Iniesta
authors.affiliation: Cancer and Human Molecular Genetics, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Serrat
authors.affiliation: Cancer and Human Molecular Genetics, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Cerón
authors.affiliation: Hereditary Cancer Programme, ICO, Girona Biomedical Research Institute (IDIBGI), Girona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Brunet
authors.affiliation: Department of Medical Oncology, ICO, IDIBGI, Girona, Spain.
authors.forename: M P
authors.initials: MP
authors.lastname: Barretina
authors.affiliation: Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Gil
authors.affiliation: Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Falo
authors.affiliation: Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fernández
authors.affiliation: Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Morilla
authors.affiliation: Department of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Pernas
authors.affiliation: Department of Gynecology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Plà
authors.affiliation: Department of Pathology, Parc Taulí Hospital Consortium, Sabadell, Barcelona, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Andreu
authors.affiliation: Medical Oncology Service, Parc Taulí Hospital Consortium, Sabadell, Barcelona, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Seguí
authors.affiliation: Department of Radiation Oncology, University Hospital Germans Trias i Pujol, ICO, Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Ballester
authors.affiliation: Department of Pathology, University Hospital Germans Trias i Pujol, ICO, IGTP, Badalona, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Castellà
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Nellist
authors.affiliation: Hospital Arnau de Vilanova, University of Lleida, Biomedical Research Institute of Lleida (IRB Lleida), Lleida, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Morales
authors.affiliation: Hospital Arnau de Vilanova, University of Lleida, Biomedical Research Institute of Lleida (IRB Lleida), Lleida, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Valls
authors.affiliation: Hospital Arnau de Vilanova, University of Lleida, Biomedical Research Institute of Lleida (IRB Lleida), Lleida, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Velasco
authors.affiliation: Hospital Arnau de Vilanova, University of Lleida, Biomedical Research Institute of Lleida (IRB Lleida), Lleida, Spain.
authors.forename: X
authors.initials: X
authors.lastname: Matias-Guiu
authors.affiliation: Angiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Figueras
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: J V
authors.initials: JV
authors.lastname: Sánchez-Mut
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Sánchez-Céspedes
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Cordero
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Gómez-Miragaya
authors.affiliation: 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.
authors.forename: L
authors.initials: L
authors.lastname: Palomero
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Gómez
authors.affiliation: Departments of Pathology and Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: T F
authors.initials: TF
authors.lastname: Gajewski
authors.affiliation: Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
authors.forename: E E W
authors.initials: EEW
authors.lastname: Cohen
authors.affiliation: Department of Pathology, Military Institute of Medicine, Warsaw, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Jesiotr
authors.affiliation: Department of Oncology, Military Institute of Medicine, Warsaw, Poland.
authors.forename: L
authors.initials: L
authors.lastname: Bodnar
authors.affiliation: Breast Cancer Clinical Research Unit, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Quintela-Fandino
authors.affiliation: Department of Experimental and Health Sciences, Barcelona Biomedical Research Park, Pompeu Fabra University (UPF), Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: López-Bigas
authors.affiliation: Department of Biochemistry and Molecular Biology, University Institute of Oncology of Asturias, University of Oviedo, Oviedo, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Valdés-Mas
authors.affiliation: Department of Biochemistry and Molecular Biology, University Institute of Oncology of Asturias, University of Oviedo, Oviedo, Spain.
authors.forename: X S
authors.initials: XS
authors.lastname: Puente
authors.affiliation: Angiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Viñals
authors.affiliation: Angiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: O
authors.initials: O
authors.lastname: Casanovas
authors.affiliation: Angiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Graupera
authors.affiliation: Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Hernández-Losa
authors.affiliation: Department of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Ramón Y Cajal
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.
authors.forename: L
authors.initials: L
authors.lastname: García-Alonso
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Saez-Rodriguez
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.|Department of Physiological Sciences II, School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Molecular and Translational Oncology Laboratory, Biomedical Research Center CELLEX-CRBC, Biomedical Research Institute 'August Pi i Sunyer' (IDIBAPS), and Systems Biology Department, Faculty of Science and Technology, University of Vic, Central University of Catalonia, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Sierra
authors.affiliation: Center for Cooperative Research in Biosciences (CIC bioGUNE), Derio, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Martín-Martín
authors.affiliation: Neuro-Oncology Section, Oncology Department, Biodonostia Research Institute, San Sebastian, Spain.|Ikerbasque, Basque Foundation for Science, Bilbao, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Matheu
authors.affiliation: Center for Cooperative Research in Biosciences (CIC bioGUNE), Derio, Spain.|Ikerbasque, Basque Foundation for Science, Bilbao, Spain.|Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV/EHU), Bilbao, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Carracedo
authors.affiliation: Cancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: González-Suárez
authors.affiliation: Department of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nanjundan
authors.affiliation: Department of Medical Oncology, VHIO, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Cortés
authors.affiliation: Hereditary Cancer Programme, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Lázaro
authors.affiliation: Centre for Applied Medical Research (CIMA) and Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Odero
authors.affiliation: Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
authors.forename: J W M
authors.initials: JWM
authors.lastname: Martens
authors.affiliation: Department of Biochemistry, Autonomous University of Madrid (UAM), Biomedical Research Institute 'Alberto Sols' (Spanish National Research Council (CSIC)-UAM), Translational Research Laboratory, Hospital La Paz Institute for Health Research (IdiPAZ), and MD Anderson International Foundation, Madrid, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Moreno-Bueno
authors.affiliation: Department of Radiation Oncology, New York University School of Medicine, New York, NY, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Barcellos-Hoff
authors.affiliation: Chemoresistance and Predictive Factors Laboratory, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Oncology Program, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: R R
authors.initials: RR
authors.lastname: Gomis
authors.affiliation: 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.
authors.forename: M A
authors.initials: MA
authors.lastname: Pujana
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D061986:MCF-7 Cells; D000074008:MDS1 and EVI1 Complex Locus Protein; D008840:Microfilament Proteins / Q000235:genetics; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015676:Osteonectin / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics*; D000076223:Regulatory-Associated Protein of mTOR; D055758:SOX9 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C502658:FSCN1 protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D008840:Microfilament Proteins; D015676:Osteonectin; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C577241:SPARC protein, human; D014157:Transcription Factors; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases