Tazarotene-induced gene 1 (TIG1) is a retinoid acid receptor-responsive gene involved in cell differentiation and tumorigenesis. Aberrant methylation of CpG islands in the TIG1 promoter is found in multiple cancers. Currently, the exact mechanism underlying the anticancer effect of TIG1 is unknown. Here, we show that TIG1 interacts with cathepsin V (CTSV), which reduces CTSV stability and subsequently affects the production of activated urokinase-type plasminogen activator (uPA), an epithelial–mesenchymal transition-associated protein. Ectopic expression of CTSV increased the expression of activated uPA and the number of migrated and invaded cells, whereas ectopic TIG1 expression reversed the effects of CTSV on the uPA signaling pathway. Similar patterns in the production of activated uPA and number of migrated and invaded cells were also observed in TIG1-expressing and CTSV-knockdown cells. The results suggest that CTSV may participate in TIG1-regulated uPA activity and the associated downstream signaling pathway.

他扎罗汀诱导的基因1（TIG1）是一种类维生素A受体响应基因，参与细胞分化和肿瘤发生。在多种癌症中发现了TIG1启动子中CpG岛的异常甲基化。目前，TIG1抗癌作用的确切机制尚不清楚。在这里，我们显示TIG1与组织蛋白酶V（CTSV）相互作用，这降低了CTSV的稳定性，并随后影响了激活的尿激酶型纤溶酶原激活剂（uPA）（一种上皮-间质转化相关蛋白）的产生。CTSV的异位表达增加了激活的uPA的表达以及迁移和侵袭细胞的数量，而异位的TIG1表达则逆转了CTSV对uPA信号通路的影响。在表达TIG1的细胞和CTSV敲低的细胞中也观察到了类似的激活uPA产生方式以及迁移和侵袭的细胞数量。结果表明CTSV可能参与TIG1调节的uPA活性和相关的下游信号通路。