Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, United States.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, United States.
Semin Cancer Biol. 2022 Oct;85:95-106. doi: 10.1016/j.semcancer.2021.04.008. Epub 2021 Apr 20.
Notch receptors participate in a conserved pathway in which ligands expressed on neighboring cells trigger a series of proteolytic cleavages that allow the intracellular portion of the receptor to travel to the nucleus and form a short-lived transcription complex that turns on target gene expression. The directness and seeming simplicity of this signaling mechanism belies the complexity of the outcomes of Notch signaling in normal cells, which are highly context and dosage dependent. This complexity is reflected in the diverse roles of Notch in cancers of various types, in which Notch may be oncogenic or tumor suppressive and may have a wide spectrum of effects on tumor cells and stromal elements. This review provides an overview of the roles of Notch in cancer and discusses challenges to clinical translation of Notch targeting agents as well as approaches that may overcome these hurdles.
Notch 受体参与保守途径，相邻细胞表达的配体触发一系列蛋白水解裂解，使受体的细胞内部分到达细胞核并形成短暂的转录复合物，从而激活靶基因表达。这种信号转导机制的直接性和看似简单性掩盖了 Notch 信号在正常细胞中的结果的复杂性，这些结果高度依赖于上下文和剂量。这种复杂性反映在 Notch 在各种类型癌症中的多种作用中，其中 Notch 可能具有致癌或肿瘤抑制作用，并且可能对肿瘤细胞和基质成分产生广泛的影响。本文综述了 Notch 在癌症中的作用，并讨论了 Notch 靶向药物临床转化的挑战以及可能克服这些障碍的方法。
