SCI REP-UK:乳腺癌基底亚型中,乳腺癌干细胞的转录因子网络可以控制免疫应答

2017-06-07 MedSci MedSci原创

乳腺癌是全世界妇女中最常见的癌症,并且癌细胞的转移是该疾病相关的最主要死亡原因。乳腺癌干细胞(bCSC)则被认为负责癌细胞的转移和形成化学耐药性。我们的研究结果指出了,存在于免疫监测和乳腺癌EMT活化之间的平衡的潜在的分子机制。这种分子机制可能对开发新的靶标治疗有重要意义。

乳腺癌是全世界妇女中最常见的癌症,并且癌细胞的转移是该疾病相关的最主要死亡原因。乳腺癌干细胞(bCSC)则被认为负责癌细胞的转移和形成化学耐药性。但是,目前乳腺癌干细胞(bCSC)的定义仍在争论之中。对乳腺干细胞的鉴别和分离依赖于几种乳腺CSC生物标志物和一些方法,如流式细胞术,体内致瘤模型,和组织学免疫染色等。

在这项研究中,我们基于推定的bCSC的全转录组分析和转录控制网络的逆向工程,我们鉴定了与该表型相关的两个网络。其中一个是由SNAI2,TWIST1,BNC2,PRRX1和TBX5控制的,并且形成间叶细胞或CSC样表型。第二个网络由相当于免疫应答调节剂的转录因子SCML4,ZNF831,SP140和IKZF3控制。免疫反应网络的表达与化疗的病理反应相关,并且,在基底亚型中与更好的无复发生存率相关。在患者来源的异种移植物中,这些网络在患者肿瘤中的表达预示着移植成功。因此,我们的研究结果指出了,存在于免疫监测和乳腺癌EMT活化之间的平衡的潜在的分子机制。这种分子机制可能对开发新的靶标治疗有重要意义。

原文出处:

W. A. da Silveira,S. du Manoir,D. G. Tiezzi,et al.Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype.[J].Scientific Reports.2017 June 7.DOI:10.1038/s41598-017-02761-6

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    2018-02-12 mjldent
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