Wnt信号通路抑制因子SFRPs在肿瘤发生发展中的研究进展

摘要

According to their different mechanisms of action, the extracellular antagonists of Wnt signaling pathway can be divided into two categories that can prevent the ligand-receptor interactions. One includes the secreted frizzled-related protein family ( SFRPs ), WIF-1 ( the Wnt inhibitory factor-1 ) and cerberus, mainly connecting the Wnt proteins to change the capacity of Wnt binding Wnt receptor complex. The other contains some members of the Dickkopf ( DKK ) family, combining low-density lipoprotein receptor-related protein 5/6 ( LRP5/6 ) to inhibit the Wnt signaling pathway. Recently, a series of studies on the inactivation mechanism of Wnt antagonist SFRPs family in malignant tumors have shown that SFRPs as a tumor suppressor gene, when epigenetic changes occurred, such as promoter methylation changes, could cause gene silence and down regulation of SFRPs, so that the abnormal Wnt pathway activation induced tumorigenesis. In this review, we will focus on the relation between SFRPs family and the Wnt signaling pathway inactivation in tumor research.%Wnt拮抗剂可以阻止配体-受体的相互作用,根据其不同的作用机制可以分为2类:一类包括分泌型卷曲相关蛋白家族(secreted frizzled-related proteins family,SFRPs)、WIF-1 (Wnt inhibitory factor-1)和Cerberus,主要是通过与Wnt蛋白结合从而改变Wnt与Wnt受体复合物结合的能力;另一类包含DKK家族(Dickkopf family)中的某些成员,通过结合低密度脂蛋白受体相关蛋白5/6(low-density lipoprotein receptor-related protein 5/6,LRP5/6)来抑制Wnt信号通路.近年来,国内外对Wnt拮抗剂SFRPs家族在恶性肿瘤的失活机制进行的一系列研究表明,SFRPs作为抑癌基因,当它发生表观遗传学改变,如启动子甲基化改变,可致基因沉默和SFRPs表达下调,使Wnt通路异常活化而诱导肿瘤发生.文中就SFRPs家族分子与Wnt信号转导失活在肿瘤中的研究作一综述.