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

Autor: Krishina Ratna Sousa de Oliveira, Sandra Martha Gomes Dias, Marcelo Falsarella Carazzolle, Carolline Fernanda Rodrigues Ascenção, Larissa Menezes dos Reis, Douglas Adamoski, Marília M. Dias, Melissa Quintero, Kaliandra de Almeida Gonçalves
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Proteomics
Cancer Research
Therapeutic target
Triple Negative Breast Neoplasms
Bioinformatics
lcsh:RC254-282
Transcriptome
03 medical and health sciences
Breast cancer
Growth factor receptor
Triple-negative breast cancer
GTP-Binding Proteins
Cell Line
Tumor
Progesterone receptor
Genetics
medicine
Humans
Computer Simulation
Epidermal growth factor receptor
RNA-Seq
Transcriptomics
Cell Proliferation
biology
business.industry
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
DNA Methylation
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Up-Regulation
ErbB Receptors
Gene Expression Regulation
Neoplastic
030104 developmental biology
MRNA Sequencing
Oncology
DNA methylation
Cancer research
biology.protein
Female
Gene expression
business
Research Article
Zdroj: BMC Cancer, Vol 17, Iss 1, Pp 1-16 (2017)
BMC Cancer
ISSN: 1471-2407
DOI: 10.1186/s12885-017-3726-2
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12885-017-3726-2) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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