文章：

FOXC1作为基底样乳腺癌治疗靶点的评价

Evaluation of FOXC1 as a therapeutic target for basal-like breast cancer 

原文发布日期：2018-03-06 

英文摘要：

Basal-like breast cancer (BLBC) is a malignant carcinoma with aggressive motility and rapid growth. Accounting for 15% of breast cancers, BLBC often exhibits a poor prognosis and tends to metastasize to the brain and lungs. Because most BLBC display a triple-negative phenotype (ER-, PR-, and HER2-), conventional cytotoxic chemotherapy remains the only treatment option despite poor success and high rate of relapse. The overexpression of the forkhead-box transcription factor C1 (FOXC1) was recently identified as a biomarker of BLBC. Increased expression of FOXC1 was linked to excessive mobility and growth of BLBC cell lines, suggesting FOXC1 as a therapeutic target. In this study, siRNA-mediated knockdown of FOXC1 was confirmed to decrease the proliferation rate, migration, and invasion in a model BLBC-like cell line (4T1). 4T1 and 4T1-∆FOXC1 cells lacking FOXC1 expression (generated by CRISPR/Cas9) were used to evaluate the effects of FOXC1 expression in an orthotopic murine model of BLBC. No statistically significant difference in tumor volume was observed between 4T1 and 4T1-∆FOXC1 tumors. Furthermore, tumors metastasized to the liver and lungs to a similar degree regardless of FOXC1 expression. These data suggest that, despite positive results in vitro, FOXC1 may not be a promising therapeutic target for BLBC. 

摘要翻译： 

基底样乳腺癌（BLBC）是一种具有侵袭性强、生长迅速的恶性癌变。该亚型占乳腺癌总数的15%，通常预后较差，且易发生脑部和肺部转移。由于大多数BLBC呈现三阴性表型（雌激素受体阴性、孕激素受体阴性和HER2阴性），传统细胞毒性化疗仍是唯一治疗选择，但疗效不佳且复发率高。近期研究发现叉头框转录因子C1（FOXC1）的过表达可作为BLBC的生物标志物。FOXC1表达增强与BLBC细胞系的过度迁移和生长相关，提示其可能成为治疗靶点。本研究通过siRNA介导的FOXC1敲低实验，在BLBC模型细胞系（4T1）中证实其可降低增殖速率、迁移和侵袭能力。采用CRISPR/Cas9技术构建FOXC1缺失的4T1细胞（4T1-∆FOXC1），通过原位小鼠BLBC模型评估FOXC1表达的影响。结果显示：4T1与4T1-∆FOXC1移植瘤的体积无统计学显著差异；不论FOXC1表达状态如何，肿瘤在肝脏和肺部的转移程度均相似。这些数据表明，尽管体外实验取得阳性结果，FOXC1可能并非BLBC的理想治疗靶点。

原文链接：

Evaluation of FOXC1 as a therapeutic target for basal-like breast cancer