Department of Infectious Diseases, Melbourne Medical School, University of Melbourne, Melbourne, VIC, Australia.
The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Handb Exp Pharmacol. 2021;269:251-277. doi: 10.1007/164_2021_524.
Frizzled activates β-catenin-dependent and β-catenin-independent Wnt signalling pathways, is highly conserved through evolution from the ancient phylum hydra to man, plays essential roles in stem cells, tissue homeostasis and regeneration in the adult, and is upregulated in diverse cancers. Much of what is known about the core components of the Wnt signalling pathways was derived from studying the function of Frizzled orthologues in the development of lower organism. As we interrogate Frizzled signalling and function for therapeutic targeting in cancer, it is timely to revisit lower organisms to gain insight into the context dependent and dynamic nature of Wnt signalling for effective drug design.
卷曲激活β-连环蛋白依赖和非依赖的 Wnt 信号通路，从古生动物门水螅到人高度保守，在干细胞、组织内稳态和成年组织再生中发挥重要作用，并在多种癌症中上调。我们对 Wnt 信号通路核心成分的了解大多来自于研究低等生物中卷曲同源物在发育中的功能。当我们为癌症的治疗靶向而探究卷曲信号和功能时，及时回顾低等生物有助于深入了解 Wnt 信号的上下文相关和动态特性，从而进行有效的药物设计。
