School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Handb Exp Pharmacol. 2021;269:175-213. doi: 10.1007/164_2021_533.
Since the discovery of the proto-oncogene Wnt1 (Int1) in 1982, WNT signaling has been identified as one of the most important pathways that regulates a wide range of fundamental developmental and physiological processes in multicellular organisms. The canonical WNT signaling pathway depends on the stabilization and translocation of β-catenin and plays important roles in development and homeostasis. The WNT/planar cell polarity (WNT/PCP) signaling, also known as one of the β-catenin-independent WNT pathways, conveys directional information to coordinate polarized cell behaviors. Similar to WNT/β-catenin signaling, disruption or aberrant activation of WNT/PCP signaling also underlies a variety of developmental defects and cancers. However, the pharmacological targeting of WNT/PCP signaling for therapeutic purposes remains largely unexplored. In this review, we briefly discuss WNT/PCP signaling in development and disease and summarize the known drugs/inhibitors targeting this pathway.
自 1982 年发现原癌基因 Wnt1（Int1）以来，WNT 信号通路已被确定为调节多细胞生物中广泛的基本发育和生理过程的最重要途径之一。经典的 WNT 信号通路依赖于 β-连环蛋白的稳定和转位，并在发育和动态平衡中发挥重要作用。WNT/平面细胞极性（WNT/PCP）信号通路，也称为β-连环蛋白非依赖性 WNT 途径之一，向细胞传递定向信息以协调极化细胞行为。与 WNT/β-连环蛋白信号通路类似，WNT/PCP 信号通路的破坏或异常激活也导致多种发育缺陷和癌症。然而，针对 WNT/PCP 信号通路的药理学靶向治疗在很大程度上仍未得到探索。在这篇综述中，我们简要讨论了 WNT/PCP 信号通路在发育和疾病中的作用，并总结了针对该通路的已知药物/抑制剂。
