转录因子brachyury,带有DNA结合T结构域,通过与各种生物中高度保守的回文共有序列结合来调节后中胚层的形成和脊索的发育。在大多数成人正常组织中不存在短枝表达和唯一的肿瘤特异性表达提供了被发展成为癌症中的新颖且有前景的诊断和治疗靶标的潜力。作为脊索瘤诊断的敏感和特异性标志物,短尾蛋白在各种研究中已被证实参与脊索瘤和几种上皮癌的发生和发展过程,但是Brachyury促进肿瘤细胞迁移的机制,侵袭和转移仍然不清楚。为此,我们试图总结短尾转录的上游调节途径和短尾激活的下游控制网络的文献,所有这些都涉及胚胎发育和肿瘤进展。我们提出了短尾表达与肿瘤进展的各自相关性,远处转移,几种类型肿瘤样本的生存率和预后(包括脊索瘤,肺癌,乳腺癌,和前列腺癌),并总结了各种短枝功能获得和功能丧失实验,以探讨其在体外各肿瘤细胞系中的特异性作用。此外,我们还讨论了另外两个与短肢功能有关的程序:上皮-间质转化(EMT)和细胞周期控制,两者都涉及短尾对肿瘤细胞生物学行为的调节。这篇综述将概述主转录因子brachyury的功能,比较其作用在胚胎发育和癌变之间的异同,并列出短尾疗法有可能帮助控制晚期癌症人群的证据。
Transcription factor
brachyury, with a DNA-binding T-domain, regulates posterior mesoderm formation and notochord development through binding with highly conserved palindromic consensus sequence in a variety of organisms. The absence of
brachyury expression in majority of adult normal tissues and exclusive tumor-specific expression provides the potential to be developed into a novel and promising diagnostic and therapeutic target in cancer. As a sensitive and specific marker in the diagnosis of chordoma,
brachyury protein has been verified to involve in the process of carcinogenesis and progression of chordoma and several epithelial carcinomas in various studies, but the mechanism by which brachyury promotes tumor cells migrate, invade and metastasis still remains less clear. To this end, we attempt to summarize the literature on the upstream regulatory pathway of brachyury transcription and downstream controlling network by
brachyury activation, all of which involve in both the embryonic development and tumor progression. We present the respective correlation of
brachyury expression with tumor progression, distant metastasis, survival rate and prognosis in several types of tumor samples (including chordoma, lung cancer, breast carcinoma, and prostate cancer), and various brachyury gain-of-function and loss-of-function experiments are summarized to explore its specific role in respective tumor cell line in vitro. In addition, we also discuss another two programs relating to brachyury function: epithelial-to-mesenchymal transition (EMT) and cell cycle control, both of which implicate in the regulation of brachyury on biological behavior of tumor cells. This review will provide an overview of the function of master transcriptional factor brachyury, compare the similarities and differences of its role between embryonic development and carcinogenesis, and list the evidence on which brachyury-target therapies have the potential to help control advanced cancer populations.