文章：

实体肿瘤中的Notch信号：一切都有一点，但不是一直都有

Notch signalling in solid tumours: a little bit of everything but not all the time

原文发布日期：2011-04-14

DOI: 10.1038/nrc3035

类型: Review Article

开放获取: 否

要点：

1. A causative role for Notch signalling is well established in T cell acute lymphoblastic leukaemias (T-ALLs), which have activating mutations in the Notch genes resulting in a constitutively active pathway. By contrast, solid tumours, which have ample opportunity to activate the pathway, exhibit inappropriate activation by multiple mechanisms, such as overexpression of ligand or loss of negative regulators of the pathway.
2. The role of Notch signalling in solid tumours is highly dependent on the spatial and temporal context of Notch activation, as well as the status of other signalling pathways in the cells.
3. Notch signalling has opposing roles in tumorigenesis depending on the cell type. Opposite interactions of the Notch pathway have been documented with the WNT and p53 pathways. Although synergy with WNT and antagonism of the p53 pathway directs the oncogenic role of Notch, the opposite is seen in the tumour suppressor context.
4. Notch signalling has a major role in the maintenance and progression of tumours by promoting epithelial to mesenchymal transition (EMT) and angiogenesis. It also confers resistance to radiation and chemotherapeutic agents.
5. The knowledge of the extensive crosstalk of the Notch pathway with other pathways such as the epidermal growth factor receptor (EGFR) pathway could prove useful in developing combinatorial cancer therapies.

要点翻译：

1. Notch信号在T细胞急性淋巴细胞白血病（T-ALL）中的致病作用已明确，该疾病因Notch基因激活突变导致信号通路持续活跃。相比之下，实体瘤虽有多重机会激活该通路，却通过多种机制呈现异常活化，如配体过表达或通路负调控因子的缺失。
2. Notch信号在实体瘤中的作用高度依赖于其激活的时空背景，以及细胞内其他信号通路的状态。
3. Notch信号在肿瘤发生中具有双重作用，具体取决于细胞类型。研究已记录Notch通路与WNT和p53通路存在相悖的相互作用：虽然与WNT的协同作用及对p53通路的拮抗作用导向Notch的致癌功能，但在抑癌背景下则呈现相反模式。
4. Notch信号通过促进上皮间质转化（EMT）和血管生成，在肿瘤的维持与进展中发挥重要作用。同时它还会介导对放疗和化疗药物的耐药性。
5. 对Notch通路与表皮生长因子受体（EGFR）等其他通路广泛交叉对话的认知，可能为开发联合癌症治疗方案提供重要依据。

英文摘要：

The discovery of Notch in Drosophila melanogaster nearly a century ago opened the door to an ever-widening understanding of cellular processes that are controlled or influenced by Notch signalling. As would be expected with such a pleiotropic pathway, the deregulation of Notch signalling leads to several pathological conditions, including cancer. A role for Notch is well established in haematological malignancies, and more recent studies have provided evidence for the importance of Notch activity in solid tumours. As it is thought to act as an oncogene in some cancers but as a tumour suppressor in others, the role of Notch in solid tumours seems to be highly context dependent.

摘要翻译： 

黑腹果蝇中Notch的发现近一个世纪前开启了通往对受Notch信号控制或影响的细胞过程不断拓宽理解的大门。正如对这样一个多效性通路所预期的那样，Notch信号的失调导致多种病理状况，包括癌症。Notch在血液系统恶性肿瘤中的作用已得到充分确立，而更近的研究则提供了Notch活性在实体瘤中重要性的证据。由于它被认为在某些癌症中充当癌基因，而在另一些癌症中则充当肿瘤抑制因子，Notch在实体瘤中的作用似乎高度依赖于具体情境。

原文链接：

Notch signalling in solid tumours: a little bit of everything but not all the time