文章：

Notch作为肿瘤抑制因子

Notch as a tumour suppressor

原文发布日期：2017-02-03

DOI: 10.1038/nrc.2016.145

类型: Review Article

开放获取: 否

要点：

1. Notch signalling can be either oncogenic or tumour suppressive depending on the tissue and/or cellular context.
2. Notch signalling is tumour suppressive for various solid tumours, including squamous cell carcinoma in several epithelial tissues, subtypes of brain cancer, liver cancer and small-cell lung cancer.
3. Loss of Notch signalling can result in perturbed regulation of cell fate decisions in stem and progenitor cells, resulting in tumour development.
4. Loss of Notch signalling can also lead to stromal remodelling and the generation of a pro-tumorigenic microenvironment that promotes carcinogenesis.

要点翻译：

1. Notch信号根据组织和/或细胞环境的不同，既可发挥促癌作用，也可发挥抑癌作用。
2. 对于多种实体肿瘤，Notch信号具有抑癌功能，包括多个上皮组织的鳞状细胞癌、脑癌亚型、肝癌和小细胞肺癌。
3. Notch信号缺失可能导致干细胞和祖细胞命运决定的调控紊乱，从而引发肿瘤发生。
4. Notch信号缺失还可导致基质重塑，形成促进癌发生的肿瘤微环境。

英文摘要：

The Notch signalling cascade is an evolutionarily conserved pathway that has a crucial role in regulating development and homeostasis in various tissues. The cellular processes and events that it controls are diverse, and continued investigation over recent decades has revealed how the role of Notch signalling is multifaceted and highly context dependent. Consistent with the far-reaching impact that Notch has on development and homeostasis, aberrant activity of the pathway is also linked to the initiation and progression of several malignancies, and Notch can in fact be either oncogenic or tumour suppressive depending on the tissue and cellular context. The Notch pathway therefore represents an important target for therapeutic agents designed to treat many types of cancer. In this Review, we focus on the latest developments relating specifically to the tumour-suppressor activity of Notch signalling and discuss the potential mechanisms by which Notch can inhibit carcinogenesis in various tissues. Potential therapeutic strategies aimed at restoring or augmenting Notch-mediated tumour suppression will also be highlighted.

摘要翻译： 

Notch信号级联是一个进化上保守的通路，在调控多种组织的发育与稳态中发挥关键作用。其控制的细胞过程与事件极为多样，数十年的持续研究揭示，Notch信号的作用具有多面性且高度依赖情境。鉴于Notch对发育与稳态的深远影响，该通路的异常活性亦与多种恶性肿瘤的发生和进展相关；事实上，Notch可因组织与细胞背景不同而表现为致癌或抑癌作用。因此，Notch通路成为治疗多种癌症的重要药物靶点。本综述聚焦于Notch信号抑癌活性的最新进展，探讨其在不同组织中抑制 carcinogenesis 的潜在机制，并重点介绍旨在恢复或增强Notch介导的肿瘤抑制的潜在治疗策略。

原文链接：

Notch as a tumour suppressor