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

BMC Cancer

Research Article

Marília Meira Dias¹  Melissa Quintero¹  Kaliandra de Almeida Gonçalves¹  Sandra Martha Gomes Dias¹  Douglas Adamoski²  Carolline Fernanda Rodrigues Ascenção²  Larissa Menezes dos Reis²  Krishina Ratna Sousa de Oliveira²  Marcelo Falsarella Carazzolle³ 

[1] Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), 13083-970, Campinas, São Paulo, Brazil;Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research in Energy and Materials (CNPEM), 13083-970, Campinas, São Paulo, Brazil;Graduate Program in Genetics and Molecular Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil;Genomic and Expression Laboratory (LGE), Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil;

关键词: Breast cancer;    Triple-negative breast cancer;    Gene expression;    RNA-Seq;    Transcriptomics;    Therapeutic target;   

DOI  :  10.1186/s12885-017-3726-2

 received in 2017-01-12, accepted in 2017-10-30,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundTriple-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.MethodsIn 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.ResultsOur 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.ConclusionsWe propose that GBP1 is a new potential druggable therapeutic target for treating TNBC with enhanced EGFR expression.

【 授权许可】

CC BY   
© The Author(s). 2017