Dai Xiaofeng, Zhang Shuo, Cheng Hongye, Cai Dongyan, Chen Xiao, Huang Zhaohui
Wuxi School of Medicine, JiangNan University, Wuxi, China.
School of Biotechnology, Jiangnan University, Wuxi, China.
Front Oncol. 2019 Oct 24;9:1089. doi: 10.3389/fonc.2019.01089. eCollection 2019.
Triple negative breast cancers are aggressive, enriched with cancer stem cells, and lack effective targeted therapies with little side effects. We isolated cancer stem cells from two triple negative breast cancer cell lines via cell sorting following transcriptome sequencing, bioinformatics analysis, experimental and clinical validations, as well as functional investigations to explore genes capturing triple negative breast cancer features for improved diagnosis and therapeutics in clinics. We found that FA2H is under-expressed in triple negative breast cancers both and in clinics, and FA2H suppresses cancer stemness via inhibiting the STAT3/IL6 axis and NFkB signaling. This study reports the tumor suppressive roles of FA2H on breast cancer cells through cancer stemness control. FA2H and other candidates unveiled in this study that capture the features of cancer stem cells may contribute as diagnostic marker and/or effective therapeutic targets for improved triple negative breast cancer management.
三阴性乳腺癌具有侵袭性,富含癌症干细胞,且缺乏副作用小的有效靶向治疗方法。我们通过转录组测序、生物信息学分析、实验和临床验证以及功能研究,从两种三阴性乳腺癌细胞系中分离出癌症干细胞,以探索能够体现三阴性乳腺癌特征的基因,从而改善临床诊断和治疗。我们发现,FA2H在三阴性乳腺癌组织和临床中均表达下调,并且FA2H通过抑制STAT3/IL6轴和NFkB信号传导来抑制癌症干性。本研究报告了FA2H通过控制癌症干性对乳腺癌细胞发挥的肿瘤抑制作用。FA2H以及本研究中揭示的其他能够体现癌症干细胞特征的候选基因,可能作为诊断标志物和/或有效的治疗靶点,以改善三阴性乳腺癌的治疗。