Department of Histology and Embryology, Guangdong Medical University, Zhanjiang 524023, Guangdong, China.
Department of Medical Genetics & Cell Biology, Guangzhou Medical University, Guangzhou 511436, Guangdong, China.
Exp Cell Res. 2018 Mar 15;364(2):160-167. doi: 10.1016/j.yexcr.2018.01.039. Epub 2018 Feb 2.
FAPα is a cell surface serine protease, mainly expressed in tumor stromal fibroblasts in more than 90% of human epithelial carcinomas. Due to its almost no expression in normal tissues and its tumor-promoting effects, FAPα has been studied as a novel potential target for antitumor therapy. However, the regulation mechanism on FAPα expression is poorly understood. In this study, we found that overexpression of snail significantly increased the mRNA and protein expression levels of FAPα in malignant melanoma B16 and SK-MEL-28 cells. Overexpression of snail increased FAPα promoter activity remarkably. Snail could directly bind to FAPα promoter to regulate FAPα expression. Moreover, snail expression was positively correlated to FAPα expression in human cutaneous malignant melanoma. Furthermore, knockdown of FAPα markedly reduced snail-induced cell migration. Overall, our findings provide a novel regulation mechanism on FAPα expression and highlight the role of snail/FAPα axis as a novel target for melanoma treatment.
FAPα 是一种细胞表面丝氨酸蛋白酶，主要表达于超过 90%的人类上皮性癌肿瘤间质成纤维细胞中。由于其在正常组织中几乎不表达，且具有促进肿瘤的作用，FAPα 已被研究作为一种新型的抗肿瘤治疗的潜在靶点。然而，FAPα 表达的调控机制仍不清楚。在本研究中，我们发现，Snail 的过表达显著增加了恶性黑色素瘤 B16 和 SK-MEL-28 细胞中 FAPα 的 mRNA 和蛋白表达水平。Snail 的过表达显著增加了 FAPα 启动子活性。Snail 可以直接结合到 FAPα 启动子上，从而调节 FAPα 的表达。此外，在人类皮肤恶性黑色素瘤中，Snail 的表达与 FAPα 的表达呈正相关。此外，敲低 FAPα 显著降低了 snail 诱导的细胞迁移。总的来说，我们的研究结果提供了 FAPα 表达的新的调控机制，并强调了 snail/FAPα 轴作为黑色素瘤治疗的新靶点的作用。
