文章：

RUNX家族：癌症的发育调节因子

The RUNX family: developmental regulators in cancer

原文发布日期：2015-01-16

DOI: 10.1038/nrc3877

类型: Review Article

开放获取: 否

要点：

1. The RUNX transcription factors are key regulators of lineage specification. They are associated with major developmental pathways such as transforming growth factor-β, WNT, Indian hedgehog, Notch, receptor tyrosine kinases and mammalian STE20-like protein kinase (MST)–Yes-associated protein 1 (YAP1).
2. RUNX family members share the evolutionarily conserved Runt domain, which binds to core-binding factor-β (CBFβ) and mediates DNA binding. Tissue-specific and overlapping expression patterns indicate both exclusive and redundant roles for the three RUNX genes in humans.
3. RUNX proteins have key roles in diverse cellular processes such as cell proliferation, differentiation, senescence, apoptosis, epithelial–mesenchymal transition, inflammation, epigenetic memory and DNA repair. RUNX activities are context dependent, can be non-DNA binding and can be dramatically altered by a broad repertoire of protein interacting partners, as well as by post-translational modification events.
4. RUNX proteins exert paradoxical activities in cancer pathogenesis: they are strongly tumour suppressive in some cancers but oncogenic in others. Aberrant expression of RUNX genes is frequently observed in diverse cancer types and has been shown to have major roles in the carcinogenic process.
5. RUNX functions upstream of the ARF–p53 pathway to promote senescence and suppress RAS-induced tumorigenesis.
6. RUNX proteins collaborate with the MYC oncogene to promote lymphoma.
7. The pathogenesis of cancer in epithelial cells is profoundly affected by the dominant role of RUNX in inflammation and its impact on the tumour microenvironment.

要点翻译：

1. RUNX转录因子是细胞谱系定向的关键调控因子。它们与多种重要发育通路相关，如转化生长因子-β、WNT、印度刺猬因子、Notch、受体酪氨酸激酶以及哺乳动物STE20样蛋白激酶（MST）-Yes相关蛋白1（YAP1）信号通路。
2. RUNX家族成员均具有进化保守的Runt结构域，该结构域可与核心结合因子β（CBFβ）结合并介导DNA结合。组织特异性及重叠性表达模式表明，人类三种RUNX基因既具有独特功能，也存在功能冗余。
3. RUNX蛋白在细胞增殖、分化、衰老、凋亡、上皮-间质转化、炎症反应、表观遗传记忆及DNA修复等多种细胞进程中发挥关键作用。其活性具有环境依赖性，可不依赖DNA结合，并能通过大量蛋白质相互作用网络及翻译后修饰事件发生显著改变。
4. 在癌症发病机制中，RUNX蛋白表现出双重作用：在特定癌症中具有显著抑癌效果，而在其他类型中却呈现促癌特性。多种肿瘤中常观察到RUNX基因的异常表达，这些异常在致癌过程中起着重要作用。
5. RUNX通过作用于ARF-p53通路上游，促进细胞衰老并抑制RAS诱导的肿瘤发生。
6. RUNX蛋白与MYC癌基因协同作用促进淋巴瘤发展。
7. RUNX在炎症过程中的主导地位及其对肿瘤微环境的影响，深刻调控着上皮细胞的癌变进程。

英文摘要：

RUNX proteins belong to a family of metazoan transcription factors that serve as master regulators of development. They are frequently deregulated in human cancers, indicating a prominent and, at times, paradoxical role in cancer pathogenesis. The contextual cues that direct RUNX function represent a fast-growing field in cancer research and could provide insights that are applicable to early cancer detection and treatment. This Review describes how RUNX proteins communicate with key signalling pathways during the multistep progression to malignancy; in particular, we highlight the emerging partnership of RUNX with p53 in cancer suppression.

摘要翻译： 

RUNX蛋白属于一类多细胞动物转录因子家族，是发育的主调控因子。它们在人类癌症中经常失调，显示出其在癌症发生中具有重要且有时矛盾的作用。决定RUNX功能的上下文线索正成为癌症研究中快速发展的领域，可能为早期癌症检测和治疗提供洞见。本综述描述了RUNX蛋白在恶性肿瘤多步骤进展过程中如何与关键信号通路相互作用；特别是，我们强调了RUNX与p53在癌症抑制中新出现的合作关系。

原文链接：

The RUNX family: developmental regulators in cancer