Guanylate-binding protein-1 is a potential new therapeutic target for triple-negative breast cancer

• Main Authors: Melissa Quintero, Douglas Adamoski, Larissa Menezes dos Reis, Carolline Fernanda Rodrigues Ascenção, Krishina Ratna Sousa de Oliveira, Kaliandra de Almeida Gonçalves, Marília Meira Dias, Marcelo Falsarella Carazzolle, Sandra Martha Gomes Dias
• Format: Article
• Language: English
• Published: BMC 2017-11-01
• Series: BMC Cancer
• Subjects: Breast cancer; Triple-negative breast cancer; Gene expression; RNA-Seq; Transcriptomics; Therapeutic target
• Online Access: http://link.springer.com/article/10.1186/s12885-017-3726-2

Abstract Background Triple-negative breast cancer (TNBC) is characterized by a lack of estrogen and progesterone receptor expression (ESR and PGR, respectively) and an absence of human epithelial growth factor receptor (ERBB2) amplification. Approximately 15–20% of breast malignancies are TNBC. Patients with TNBC often have an unfavorable prognosis. In addition, TNBC represents an important clinical challenge since it does not respond to hormone therapy. Methods In this work, we integrated high-throughput mRNA sequencing (RNA-Seq) data from normal and tumor tissues (obtained from The Cancer Genome Atlas, TCGA) and cell lines obtained through in-house sequencing or available from the Gene Expression Omnibus (GEO) to generate a unified list of differentially expressed (DE) genes. Methylome and proteomic data were integrated to our analysis to give further support to our findings. Genes that were overexpressed in TNBC were then curated to retain new potentially druggable targets based on in silico analysis. Knocking-down was used to assess gene importance for TNBC cell proliferation. Results Our pipeline analysis generated a list of 243 potential new targets for treating TNBC. We finally demonstrated that knock-down of Guanylate-Binding Protein 1 (GBP1 ), one of the candidate genes, selectively affected the growth of TNBC cell lines. Moreover, we showed that GBP1 expression was controlled by epidermal growth factor receptor (EGFR) in breast cancer cell lines. Conclusions We propose that GBP1 is a new potential druggable therapeutic target for treating TNBC with enhanced EGFR expression.