CMU, Department for Pathology and Immunology, University of Geneva, Rue Michel Servet, 1211 Geneva 4, Switzerland.
Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Swiss Institute for Experimental Cancer Research, Lausanne, Vaud 1015, Switzerland.
Nat Rev Cancer. 2017 Mar;17(3):145-159. doi: 10.1038/nrc.2016.145. Epub 2017 Feb 3.
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.
Notch 信号级联是一条进化上保守的通路，在调节各种组织的发育和稳态方面起着关键作用。它控制的细胞过程和事件多种多样，最近几十年来的持续研究揭示了 Notch 信号的作用是多方面的，高度依赖于上下文。与 Notch 对发育和稳态的深远影响一致，该通路的异常活性也与几种恶性肿瘤的起始和进展有关，事实上， Notch 可以是致癌的，也可以是肿瘤抑制的，这取决于组织和细胞的背景。因此， Notch 通路是治疗多种癌症的治疗药物的重要靶点。在这篇综述中，我们重点介绍了与 Notch 信号的肿瘤抑制活性相关的最新进展，并讨论了 Notch 抑制各种组织发生癌变的潜在机制。还将强调旨在恢复或增强 Notch 介导的肿瘤抑制的潜在治疗策略。
