分泌型卷曲相关蛋白家族在Wnt信号通路中的双向调节作用

Wnt信号通过直接参与细胞的增殖、极化和命运特化,控制胚胎发育和成体稳态,其信号异常不仅会造成发育缺陷,而且与多种癌症和代谢性疾病的发生密切相关。分泌型卷曲相关蛋白(secreted frizzled-related proteins,sFRPs)是一种可溶性蛋白质,因其结构与Wnt信号的卷曲蛋白(frizzled,Fz)受体高度同源而被认为是一类Wnt通路拮抗剂。但随着对sFRPs家族的深入研究,发现sFRPs在Wnt信号通路传导过程中并不局限于作为一种拮抗因子,还发挥激活因子的功能。最新研究还发现,sFRPs不仅作为经典的胞外因子发挥作用,在一些肿瘤干细胞中还可进入细胞核双向调节(拮抗或激活)Wnt信号传导。本文结合最新研究,全面综述了sFRPs家族蛋白在Wnt信号传导中的双向调节作用,这有助于理解sFRPs蛋白在生物体器官发育和疾病发生中的作用。

Bidirectional Regulation of Secreted Frizzled-Related Proteins (sFRPs) in Wnt Signaling Pathway

Wnt signaling regulates embryonic development and adult homeostasis via directly participating in cell proliferation, polarization, and fate specialization. Abnormal Wnt signaling not only causes developmental defects, but also closely correlates with the occurrence of various cancers and metabolic diseases. Secreted frizzled-related proteins (sFRPs) are soluble proteins that are considered to be antagonists of Wnt signaling as their high homologies to the Frizzled (Fz) receptor of Wnt pathway. However, recent studies show that sFRPs not only act as classical antagonists but also function as activators during the Wnt signaling pathway. Moreover, the latest research finds that sFRPs are biphasic modulators of Wnt-Signaling-Elicited cancer stem cell properties beyond extracellular control. Here we review the bidirectional regulation of sFRPs in Wnt signaling comprehensively, which is helpful to understand the role of sFRPs in the embryonic development and physiological and pathological processes.