VGLL1 expression is associated with a triple-negative basal-like phenotype in breast cancer

• Published in: Endocrine-related cancer Vol. 21; no. 4; pp. 587 - 599
• Main Authors: Castilla, María Ángeles, López-García, María Ángeles, Atienza, María Reina, Rosa-Rosa, Juan Manuel, Díaz-Martín, Juan, Pecero, María Luisa, Vieites, Begoña, Romero-Pérez, Laura, Benítez, Javier, Calcabrini, Annarica, Palacios, José
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.08.2014
• Subjects: Adult; Aged; Biomarkers, Tumor - metabolism; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - metabolism; Cell Line, Tumor; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Estrogen Receptor alpha - metabolism; Female; Humans; MicroRNAs - metabolism; Middle Aged; Phenotype; RNA, Messenger - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; breast cancer; BRCA1; Vgll1; basal-like phenotype; miR-934
• DOI: 10.1530/ERC-13-0485
• ISSN: 1351-0088

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.