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Updated: Apr 28, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer
María Ángeles Castilla1, María Ángeles López-García2, María Reina Atienza3
1Instituto 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.
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.
