WNT-5A: signaling and functions in health and disease

WNT-5A plays critical roles in a myriad of processes from embryonic morphogenesis to the maintenance of post-natal homeostasis. WNT-5A knock-out mice fail to survive and present extensive structural malformations. WNT-5A predominantly activates β-catenin-independent WNT signaling cascade but can also activate β-catenin signaling to relay its diverse cellular effects such as cell polarity, migration, proliferation, cell survival, and immunomodulation. Moreover, aberrant WNT-5A signaling is associated with several human pathologies such as cancer, fibrosis, and inflammation. Thus, owing to its diverse functions, WNT-5A is a crucial signaling molecule currently under intense investigation with efforts to not only delineate its signaling mechanisms and functions in physiological and pathological conditions, but also to develop strategies for its therapeutic targeting.