ArticleOncogene2017
Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.
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In one paragraph
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
What it found
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- SOX9 drives a stem-like transcriptional state and platinum resistance in high-grade serous ovarian cancer.The Journal of clinical investigation · 2025Article
- SOX9: an important factor in regulating breast cancer.European journal of medical research · 2025Review
- The role of the mTOR pathway in breast cancer stem cells (BCSCs): mechanisms and therapeutic potentials.Stem cell research & therapy · 2025Review
- RPTOR blockade suppresses brain metastases of NSCLC by interfering the ceramide metabolism via hijacking YY1 binding.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- Fate decisions of breast cancer stem cells in cancer progression.Frontiers in oncology · 2022Review
- Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue.Molecular cancer research : MCR · 2021Article
- Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis.EMBO molecular medicine · 2021Article
- MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions.Cell death and differentiation · 2021Article
- SOX9 has distinct roles in the formation and progression of different non-small cell lung cancer histotypes.The Journal of pathology · 2021Article
- Signaling Pathways Involved in Nutrient Sensing Control in Cancer Stem Cells: An Overview.Frontiers in endocrinology · 2021Review
- SOX9: The master regulator of cell fate in breast cancer.Biochemical pharmacology · 2020Review
- Article
- SOD2 acetylation on lysine 68 promotes stem cell reprogramming in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration.Scientific reports · 2019Article
- Emerging Role of SOX Proteins in Breast Cancer Development and Maintenance.Journal of mammary gland biology and neoplasia · 2019Review
- Novel and Alternative Targets Against Breast Cancer Stemness to Combat Chemoresistance.Frontiers in oncology · 2019Review
- DLG5 suppresses breast cancer stem cell-like characteristics to restore tamoxifen sensitivity by inhibiting TAZ expression.Journal of cellular and molecular medicine · 2019Article
- High collagen density augments mTOR-dependent cancer stem cells in ERα+ mammary carcinomas, and increases mTOR-independent lung metastases.Cancer letters · 2018Article
- Ecotropic viral integration site 1 promotes metastasis independent of epithelial mesenchymal transition in colon cancer cells.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
93 authors at 20 institutions in 6 countries.
F MateoBreast 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.
E J ArenasOncology Program, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
H AguilarBreast 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.
J Serra-MusachBreast 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.
G Ruiz de GaribayBreast 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.
J BoniBreast 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.
M MaicasCentre for Applied Medical Research (CIMA) and Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain.
S DuDepartment of Radiation Oncology, New York University School of Medicine, New York, NY, USA.
F IorioEuropean Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.
C Herranz-OrsBreast 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.
A IslamDepartment of Genetic Engineering and Biotechnology, University of Dhaka, Dhaka, Bangladesh.
X PradoBreast 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.
A LlorenteBreast 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.
A PetitDepartment of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
A VidalDepartment of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
I CatalàDepartment of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
T SolerDepartment of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
G VenturasDepartment of Pathology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
A Rojo-SebastianDepartment of Pathology, MD Anderson Cancer Center, Madrid, Spain.
H SerraAngiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
D CuadrasStatistics Unit, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
I BlancoHereditary Cancer Programme, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
J LozanoDepartment 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.
F CanalsProteoRed-Instituto de Salud Carlos III, Proteomic Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona, Spain.
A M SieuwertsDepartment of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
V de WeerdDepartment of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
M P LookDepartment of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
S PuertasChemoresistance and Predictive Factors Laboratory, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
N GarcíaBreast 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.
A S PerkinsUniversity of Rochester Medical Center, School of Medicine and Dentistry, Rochester, NY, USA.
N BonifaciBreast 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.
M SkowronBreast 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.
L Gómez-BaldóBreast 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.
V HernándezBiological Clues of the Invasive and Metastatic Phenotype Laboratory, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
A Martínez-ArandaBiological Clues of the Invasive and Metastatic Phenotype Laboratory, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
M Martínez-IniestaChemoresistance and Predictive Factors Laboratory, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
X SerratCancer and Human Molecular Genetics, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
J CerónCancer and Human Molecular Genetics, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain.
J BrunetHereditary Cancer Programme, ICO, Girona Biomedical Research Institute (IDIBGI), Girona, Spain.
M P BarretinaDepartment of Medical Oncology, ICO, IDIBGI, Girona, Spain.
M GilDepartment of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
C FaloDepartment of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
A FernándezDepartment of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
I MorillaDepartment of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
S PernasDepartment of Medical Oncology, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
M J PlàDepartment of Gynecology, University Hospital of Bellvitge, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
X AndreuDepartment of Pathology, Parc Taulí Hospital Consortium, Sabadell, Barcelona, Spain.
M A SeguíMedical Oncology Service, Parc Taulí Hospital Consortium, Sabadell, Barcelona, Spain.
R BallesterDepartment of Radiation Oncology, University Hospital Germans Trias i Pujol, ICO, Germans Trias i Pujol Research Institute (IGTP), Badalona, Barcelona, Spain.
E CastellàDepartment of Pathology, University Hospital Germans Trias i Pujol, ICO, IGTP, Badalona, Barcelona, Spain.
M NellistDepartment of Clinical Genetics, Erasmus Medical Centre, Rotterdam, The Netherlands.
S MoralesHospital Arnau de Vilanova, University of Lleida, Biomedical Research Institute of Lleida (IRB Lleida), Lleida, Spain.
J VallsHospital Arnau de Vilanova, University of Lleida, Biomedical Research Institute of Lleida (IRB Lleida), Lleida, Spain.
A VelascoHospital Arnau de Vilanova, University of Lleida, Biomedical Research Institute of Lleida (IRB Lleida), Lleida, Spain.
X Matias-GuiuHospital Arnau de Vilanova, University of Lleida, Biomedical Research Institute of Lleida (IRB Lleida), Lleida, Spain.
A FiguerasAngiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
J V Sánchez-MutCancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
M Sánchez-CéspedesCancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
A CorderoCancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
J Gómez-MiragayaCancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
L PalomeroBreast 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.
A GómezCancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
T F GajewskiDepartments of Pathology and Medicine, University of Chicago, Chicago, IL, USA.
E E W CohenMoores Cancer Center, University of California San Diego, La Jolla, CA, USA.
M JesiotrDepartment of Pathology, Military Institute of Medicine, Warsaw, Poland.
L BodnarDepartment of Oncology, Military Institute of Medicine, Warsaw, Poland.
M Quintela-FandinoBreast Cancer Clinical Research Unit, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
N López-BigasDepartment of Experimental and Health Sciences, Barcelona Biomedical Research Park, Pompeu Fabra University (UPF), Barcelona, Spain.
R Valdés-MasDepartment of Biochemistry and Molecular Biology, University Institute of Oncology of Asturias, University of Oviedo, Oviedo, Spain.
X S PuenteDepartment of Biochemistry and Molecular Biology, University Institute of Oncology of Asturias, University of Oviedo, Oviedo, Spain.
F ViñalsAngiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
O CasanovasAngiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
M GrauperaAngiogenesis Research Group, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
J Hernández-LosaDepartment of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain.
S Ramón Y CajalDepartment of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain.
L García-AlonsoEuropean Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.
J Saez-RodriguezEuropean Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge, UK.
M EstellerCancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
A SierraMolecular 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.
N Martín-MartínCenter for Cooperative Research in Biosciences (CIC bioGUNE), Derio, Spain.
A MatheuNeuro-Oncology Section, Oncology Department, Biodonostia Research Institute, San Sebastian, Spain.
A CarracedoCenter for Cooperative Research in Biosciences (CIC bioGUNE), Derio, Spain.
E González-SuárezCancer Epigenetics and Biology Program (PEBC), IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
M NanjundanDepartment of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL, USA.
J CortésDepartment of Medical Oncology, VHIO, Vall d'Hebron University Hospital, Barcelona, Spain.
C LázaroHereditary Cancer Programme, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
M D OderoCentre for Applied Medical Research (CIMA) and Department of Biochemistry and Genetics, University of Navarra, Pamplona, Spain.
J W M MartensDepartment of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Cancer Genomics Centre, Rotterdam, The Netherlands.
G Moreno-BuenoDepartment 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.
M H Barcellos-HoffDepartment of Radiation Oncology, New York University School of Medicine, New York, NY, USA.
A VillanuevaChemoresistance and Predictive Factors Laboratory, ProCURE, ICO, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain.
R R GomisOncology Program, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain.
M A PujanaBreast 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.
Institut d'Investigació Biomédica de Bellvitge · ESInstitut Català d'Oncologia · ESBellvitge University Hospital · ESCancer Genomics Centre · NLEuropean Bioinformatics Institute · GBVall d'Hebron Hospital Universitari · ESInstitut d'Investigació Biomèdica de Girona · ESInstitute for Research in Biomedicine · ESNew York University · USUniversidad de Navarra · ESUniversidad de Oviedo · ESUniversitat de Lleida · ESWojskowy Instytut Medycyny Lotniczej · PLBiomedical Research Institute · USBiomedical Research Institute of Lleida · ESCIC bioGUNE · ESConsorci Institut D'Investigacions Biomediques August Pi I Sunyer · ESErasmus MC · NLErasmus University Rotterdam · NLHospital Universitari Arnau de Vilanova · ES
Funding
Wellcome Trust
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.
Indexed as
Adaptor Proteins, Signal TransducingAdultAgedBreast NeoplasmsCarrier ProteinsCell ProliferationDNA-Binding ProteinsFemaleGene Expression Regulation, NeoplasticHumansLung NeoplasmsMCF-7 CellsMDS1 and EVI1 Complex Locus ProteinMicrofilament ProteinsMiddle AgedNeoplasm MetastasisAdaptor Proteins, Signal TransducingCarrier ProteinsDNA-Binding ProteinsFSCN1 protein, humanMDS1 and EVI1 Complex Locus ProteinMECOM protein, humanMicrofilament ProteinsMTOR protein, humanOsteonectinRegulatory-Associated Protein of mTORRPTOR protein, humanSOX9 protein, humanSOX9 Transcription FactorSPARC protein, humanTOR Serine-Threonine KinasesTranscription Factors
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