Guanylate-binding protein-1 is a potential new therapeutic target for triple-negative breast cancer.
Guanylate-binding protein-1 is a potential new therapeutic target for triple-negative breast cancer.
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DOI：
10.1186/s12885-017-3726-2
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发表时间：
2017-11-07
期刊：
影响因子：
3.8
通讯作者：
Dias SMG
中科院分区：
文献类型：
--
作者：
Quintero M;Adamoski D;Reis LMD;Ascenção CFR;Oliveira KRS;Gonçalves KA;Dias MM;Carazzolle MF;Dias SMG
三阴性乳腺癌 (TNBC) 的特点是缺乏雌激素和孕激素受体表达（分别为 ESR 和 PGR）以及缺乏人上皮生长因子受体 (ERBB2) 扩增。大约 15-20% 的乳腺恶性肿瘤是 TNBC。 TNBC 患者通常预后不良。此外，TNBC 是一个重要的临床挑战，因为它对激素治疗没有反应。在这项工作中，我们整合了来自正常和肿瘤组织（从癌症基因组图谱 (TCGA) 获得）和通过内部测序获得或从基因表达综合 (GEO) 获得的细胞系的高通量 mRNA 测序 (RNA-Seq) 数据，以生成差异表达 (DE) 基因的统一列表。甲基组和蛋白质组数据被整合到我们的分析中，以进一步支持我们的发现。然后根据计算机分析对 TNBC 中过度表达的基因进行筛选，以保留新的潜在可药物靶标。敲低用于评估基因对 TNBC 细胞增殖的重要性。我们的管道分析生成了 243 个治疗 TNBC 的潜在新靶点列表。我们最终证明，候选基因之一鸟苷酸结合蛋白 1 (GBP1) 的敲低选择性地影响 TNBC 细胞系的生长。此外，我们发现乳腺癌细胞系中GBP1的表达受到表皮生长因子受体（EGFR）的控制。我们认为 GBP1 是治疗 EGFR 表达增强的 TNBC 的新的潜在药物治疗靶点。本文的在线版本 (10.1186/s12885-017-3726-2) 包含补充材料，可供授权用户使用。
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. 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. 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. We propose that GBP1 is a new potential druggable therapeutic target for treating TNBC with enhanced EGFR expression. The online version of this article (10.1186/s12885-017-3726-2) contains supplementary material, which is available to authorized users.
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