The Notch pathway has been implicated in both oncogenic and tumour-suppressive roles in cancer depending on the tissue type and cellular context. However, until recently, little was known about the pathway in bladder cancer. Studies have revealed that NOTCH1 copy number and expression are decreased in bladder cancer and NOTCH1 activation in bladder cancer cell lines reduces proliferation, suggesting that NOTCH1 acts as a tumour suppressor. Furthermore, in transgenic models, bladder cancer is promoted by bladder-specific inactivation of a component of the γ-secretase complex, which liberates the intracellular domain of neurogenic locus Notch homologue protein (NOTCH) and starts the signalling cascade. By contrast, further work has demonstrated that NOTCH2 acts as an oncogene that promotes cell proliferation and metastasis through epithelial-to-mesenchymal transition, cell cycle progression, and maintenance of stemness. Studies indicating that NOTCH1 and NOTCH2 have opposite effects on the progression of bladder cancer could give rise to potential therapeutic approaches aimed at blocking or restoring the Notch pathway.

根据组织类型和细胞情况，Notch途径与癌症的致癌作用和肿瘤抑制作用有关。但是，直到最近，人们对膀胱癌的通路知之甚少。研究表明，在膀胱癌中，NOTCH1的拷贝数和表达降低，并且在膀胱癌细胞系中的NOTCH1活化降低了增殖，这表明NOTCH1起到了抑癌作用。此外，在转基因模型中，γ-分泌酶复合物成分的膀胱特异性失活会促进膀胱癌，这会释放神经源性Notch同源蛋白（NOTCH）的细胞内结构域并启动信号级联。相比之下，进一步的工作表明NOTCH2充当致癌基因，通过上皮向间充质转化，细胞周期进程和维持干性而促进细胞增殖和转移。研究表明，NOTCH1和NOTCH2对膀胱癌的进展具有相反的作用，可能会引起潜在的旨在阻断或恢复Notch途径的治疗方法。