摘要
Brachyury是T-box基因家族的一个重要的转录因子,在胚胎的中胚层发育中有进化-保守的功能。最近的研究表明,在多种人类肿瘤中,Brachyury的过表达与上皮间质转化(EMT)相关,肿瘤转移,肿瘤干细胞标志物的表达,并对化疗和放疗产生耐受。Brachyury 诊断和预后的生物标志物,在肿瘤组织中的表达与肿瘤分级、相关阶段,侵袭,转移和预后不良有关。Brachyury阳性肿瘤细胞会靶向调节EMT的程度和停止侵袭。成纤维细胞生长因子,转化生长因子-β以及其他EMT信号因子会参与Brachyury的肿瘤发生,发展过程的分子通路。实验性的,Brachyury击倒在EMT和干细胞标记物中的表达会下调,形成肿瘤球体,最后侵袭。酵母Brachyury载体疫苗的重组治疗会激活和扩大体外Brachyury特异的CD4+和CD8+ T细胞,随着Brachyury蛋白肿瘤细胞裂解产物的表达。 进一步了解Brachyury的特点及其相关的信号通路可能有助于开发新的针对EMT治疗策略。
关键词: Brachyury;上皮间质转化;EMT;转录因子;肿瘤发生;信号通路;肿瘤疫苗。
Current Cancer Drug Targets
Title:Understanding Molecular Pathways and Targets of Brachyury in Epithelial-mesenchymal Transition (EMT) in Human Cancers
Volume: 16 Issue: 7
Author(s): Wenzhe Song and Glenda C. Gobe
Affiliation:
关键词: Brachyury;上皮间质转化;EMT;转录因子;肿瘤发生;信号通路;肿瘤疫苗。
摘要: Brachyury is an important transcription factor of the T-box gene family with an evolutionarily-conserved function in mesoderm development in the embryo. Recent research has demonstrated that, in various human carcinomas, overexpression of Brachyury is associated with epithelial-mesenchymal transition (EMT), tumor metastasis, expression of markers for cancer stem cells, and resistance to chemotherapy and radiotherapy. Brachyury is a diagnostic and prognostic biomarker, and its expression in tumor tissues is associated with increasing tumor grade, stage, invasiveness, metastasis and poor prognosis. Targeting of Brachyury-positive tumor cells may modulate the extent of EMT and stop invasiveness. Fibroblast growth factor, transforming growth factor-β and other EMT signalling factors are involved in the molecular pathways of Brachyury in tumorigenesis and development. Experimentally, Brachyury knockdown resulted in downregulation of EMT and stem cell markers, formation of tumor spheroids, and invasiveness. Treatment with recombinant yeast-Brachyury vector-based vaccine can activate and expand Brachyury-specific CD4+ and CD8+ T-cells in vitro, with an outcome of lysis of human tumor cells expressing the Brachyury protein. Further understanding of the characteristics of Brachyury and its associated signaling pathways might help in developing novel therapeutic strategies against EMT.
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Cite this article as:
Wenzhe Song and Glenda C. Gobe , Understanding Molecular Pathways and Targets of Brachyury in Epithelial-mesenchymal Transition (EMT) in Human Cancers, Current Cancer Drug Targets 2016; 16 (7) . https://dx.doi.org/10.2174/1568009616666160328113338
DOI https://dx.doi.org/10.2174/1568009616666160328113338 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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