Unleashing Wnts: Wnt ligands fuel cancer spread

Wnt signaling has long been implicated in cancer development, but recent studies have revealed new insights into how Wnt ligands themselves drive metastasis. Currently, research identifies Wnt1, Wnt2, Wnt2b, Wnt3, Wnt3a, Wnt4, Wnt5a, Wnt5b, Wnt6, Wnt8a, Wnt9b, Wnt10a, Wnt10b, and Wnt16 as pro-metastatic Wnt ligands, while Wnt7a, Wnt7b, Wnt8b, Wnt9a, and Wnt11 exhibit conflicting pro- and anti-metastatic roles. These ligands arise from diverse sources in the tumor microenvironment and perform a wide range of roles in the metastatic cascade, including epithelial-to-mesenchymal transition, matrix metalloproteinase production, cell motility, angiogenesis, cell death resistance, and mesenchymal-to-epithelial transition. Their diverse and critical roles in metastasis make Wnt ligands attractive therapeutic targets.