NOTCH1编码蛋白一种单次跨膜受体和转录因子，可以作为致癌基因和抑癌基因发挥作用。NOTCH1作为跨膜受体，参与进化上保守的细胞-细胞信号转导途径。NOTCH1受体与相邻细胞上的配体分子的相互作用导致γ-分泌酶对NOTCH1的蛋白水解切割。然后，切割的细胞内NOTCH1结构域可以激活细胞核中的基因表达并调节细胞分化，生长，增殖，存活和代谢的各个方面。NOTCH家族成员经常在各种癌症中发生突变，这些突变可能是功能获得或功能丧失突变。在T细胞急性淋巴细胞白血病（T-ALL），慢性淋巴细胞白血病和腺样囊性癌中鉴定了NOTCH1的易位和激活突变。 NOTCH1功能丧失突变在实体瘤中最常见，即鳞状细胞癌。

NOTCH1 is a transmembrane receptor that participates in an evolutionarily conserved cell-to-cell signal transduction pathway. Interaction of the NOTCH1 receptor with ligand molecules on adjacent cells results in the proteolytic cleavage of NOTCH1 by gamma-secretase. The cleaved intracellular NOTCH1 domain can then activate gene expression in the nucleus and regulate various aspects of cell differentiation, growth, proliferation, survival, and metabolism. The specific effects of NOTCH1 signaling vary depending on the cellular context. NOTCH family members are frequently mutated in a variety of cancers, and these mutations can be either gain- or loss-of-function mutations. Translocations and activating mutations in NOTCH1 have been identified in T-cell acute lymphoblastic leukemia (T-ALL), chronic lymphocytic leukemia, and adenoid cystic carcinoma. These NOTCH1 activating mutations either enhance the cleavage of NOTCH1 by gamma-secretase or extend the half-life of intracellular NOTCH1. NOTCH1 loss-of-function mutations are most common in solid tumors, namely squamous cell carcinomas, and occur as missense, frameshift or nonsense mutations in important NOTCH1 functional domains.

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