Bolós Victoria, Grego-Bessa Joaquín, de la Pompa José Luis
Departmento de Inmunología y Oncología, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Darwin 3, Campus de Cantoblanco, E-28049 Madrid, Spain.
Endocr Rev. 2007 May;28(3):339-63. doi: 10.1210/er.2006-0046. Epub 2007 Apr 4.
Notch is an evolutionarily conserved local cell signaling mechanism that participates in a variety of cellular processes: cell fate specification, differentiation, proliferation, apoptosis, adhesion, epithelial-mesenchymal transition, migration, and angiogenesis. These processes can be subverted in Notch-mediated pathological situations. In the first part of this review, we will discuss the role of Notch in vertebrate central nervous system development, somitogenesis, cardiovascular and endocrine development, with attention to the mechanisms by which Notch regulates cell fate specification and patterning in these tissues. In the second part, we will review the molecular aspects of Notch-mediated neoplasias, where Notch can act as an oncogene or as a tumor suppressor. From all these studies, it becomes evident that the outcome of Notch signaling is strictly context-dependent and differences in the strength, timing, cell type, and context of the signal may affect the final outcome. It is essential to understand how Notch integrates inputs from other signaling pathways and how specificity is achieved, because this knowledge may be relevant for future therapeutic applications.
Notch是一种进化上保守的局部细胞信号传导机制，参与多种细胞过程：细胞命运决定、分化、增殖、凋亡、黏附、上皮-间质转化、迁移和血管生成。在Notch介导的病理情况下，这些过程可能会被颠覆。在本综述的第一部分，我们将讨论Notch在脊椎动物中枢神经系统发育、体节发生、心血管和内分泌发育中的作用，重点关注Notch在这些组织中调节细胞命运决定和模式形成的机制。在第二部分，我们将综述Notch介导的肿瘤形成的分子方面，其中Notch可以作为癌基因或肿瘤抑制因子发挥作用。从所有这些研究中可以明显看出，Notch信号传导的结果严格依赖于背景，信号强度、时间、细胞类型和背景的差异可能会影响最终结果。了解Notch如何整合来自其他信号通路的输入以及如何实现特异性至关重要，因为这些知识可能与未来的治疗应用相关。
