title: VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer.
abstract: Vestigial-like 1 (VGLL1) is a poorly characterized gene encoding a transcriptional co-activator structurally homologous to TAZ and YAP that modulates the Hippo pathway in Drosophila. In this study, we examined the expression of VGLL1 and its intronic miRNA, miR-934, in breast cancer. VGLL1 and miR-934 expression miRNA profiling was carried out on frozen samples of grade 3 invasive ductal carcinomas. VGLL1 protein was also examined in 433 sporadic and BRCA1-associated breast carcinomas on tissue microarrays. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to confirm differences in VGLL1 and miR-934 expression in different breast cancer subtypes, and to correlate their expression with that of other genes and miRNAs. Of 28 miRNAs differentially expressed in estrogen receptor (ER)-positive and ER-negative grade 3 breast carcinomas, miR-934 was most strongly upregulated in ER-negative carcinomas, and its expression was correlated with that of VGLL1. Nuclear VGLL1 expression was observed in 13% of sporadic breast carcinomas, and while VGLL1 was only occasionally found in luminal A (0.70%) and B (5.60%) carcinomas, it was often expressed in HER2-positive (17%), triple-negative (TN) breast carcinomas (>40%) and BRCA1-associated TN carcinomas (>50%). These findings were confirmed in the TCGA dataset, which revealed positive associations with luminal progenitor genes (GABRP, SLC6A14, FOXC1, PROM1, and BBOX1) and strong negative correlations with ER-associated genes (ESR1, C6ORF211, GATA3, and FOXA1). Moreover, VGLL1 expression was associated with reduced overall survival. In conclusion, VGLL1 and miR-934 are mainly expressed in sporadic and BRCA1-associated TN basal-like breast carcinomas, and their coordinated expression, at least partially mediated by the direct modulation of ESR1, might be involved in the maintenance of a luminal progenitor phenotype.
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, ItalyInstituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy jose.palacios@salud.madrid.org macastillamoro@gmail.com.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Castilla
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, ItalyInstituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: López-García
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy.
authors.forename: María Reina
authors.initials: MR
authors.lastname: Atienza
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Rosa-Rosa
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, ItalyInstituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy.
authors.forename: Juan
authors.initials: J
authors.lastname: Díaz-Martín
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy.
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Pecero
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, ItalyInstituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy.
authors.forename: Begoña
authors.initials: B
authors.lastname: Vieites
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, ItalyInstituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Romero-Pérez
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy.
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy.
authors.forename: Annarica
authors.initials: A
authors.lastname: Calcabrini
authors.affiliation: Instituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, ItalyInstituto de Biomedicina de Sevilla-CSIC-Universidad de SevillaHospital Universitario Virgen del Rocío, Department of Pathology, Avda. Manuel Siurot S/N, 41013 Seville, SpainRed Temática de Investigación Cooperativa en Cáncer (RTICC)ISCIII, Madrid, SpainServicio de Anatomía PatológicaHospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, SpainHuman Genetics GroupDepartamento de Biología del Cáncer, Spanish National Cancer Research Centre (CNIO)-CIBERER, Madrid, SpainDepartment of Technology and HealthIstituto Superiore di Sanità, Rome, Italy jose.palacios@salud.madrid.org macastillamoro@gmail.com.
authors.forename: José
authors.initials: J
authors.lastname: Palacios
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D035683:MicroRNAs; D012333:RNA, Messenger; D014157:Transcription Factors; C400682:VGLL1 protein, human
keywords: BRCA1; Vgll1; basal-like phenotype; breast cancer; miR-934