Guanylate-binding Protein-1 is a Potential New Therapeutic Target for Triple-negative Breast Cancer

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2017 Nov 9

PMID 29115931

Citations 25

Authors

Melissa Quintero

Douglas Adamoski

Larissa Menezes Dos Reis

Carolline Fernanda Rodrigues Ascencao

Krishina Ratna Sousa de Oliveira

Kaliandra de Almeida Goncalves

Marilia Meira Dias

Marcelo Falsarella Carazzolle

Sandra Martha Gomes Dias

Affiliations

Soon will be listed here.

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.

Citing Articles

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