Chen Ming, Wu Yinghui, Zhang Hong, Li Suoyuan, Zhou Jundong, Shen Jun
Department of Orthopeadic Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
Department of Orthopeadic Surgery, Wuxi No. 2 People's Hospital, Nanjing Medical University, Wuxi, China.
Front Oncol. 2020 Jun 30;10:961. doi: 10.3389/fonc.2020.00961. eCollection 2020.
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 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.
转录因子短尾（brachyury）具有一个DNA结合T结构域，通过与多种生物体中高度保守的回文共有序列结合来调节后中胚层形成和脊索发育。在大多数成年正常组织中缺乏短尾表达以及其在肿瘤中特异性表达，使其有潜力成为一种新型且有前景的癌症诊断和治疗靶点。作为脊索瘤诊断中的一种敏感且特异的标志物，在各项研究中已证实短尾蛋白参与了脊索瘤以及几种上皮癌的致癌过程和进展，但是短尾促进肿瘤细胞迁移、侵袭和转移的机制仍不太清楚。为此，我们试图总结关于短尾转录上游调控途径以及短尾激活后的下游控制网络的文献，这些都涉及胚胎发育和肿瘤进展。我们展示了短尾表达与几种肿瘤样本（包括脊索瘤、肺癌、乳腺癌和前列腺癌）的肿瘤进展、远处转移、生存率和预后的各自相关性，并总结了各种短尾功能获得和功能丧失实验，以探索其在各自肿瘤细胞系中的具体作用。此外，我们还讨论了与短尾功能相关的另外两个过程：上皮-间质转化（EMT）和细胞周期控制，这两者都暗示了短尾对肿瘤细胞生物学行为的调节作用。本综述将概述主要转录因子短尾的功能，比较其在胚胎发育和致癌过程中作用的异同，并列出短尾靶向治疗有可能帮助控制晚期癌症人群的证据。
