Wnt5a is a secreted glycoprotein, belonging to the non-canonical Wnt family. It binds to Frizzled (FZD) and Receptor Tyrosine Kinase-Like Orphan Receptor (ROR) family members, activating non-canonical Wnt signaling pathways. Wnt5a is involved in diverse cellular processes such as proliferation, differentiation, migration, adhesion, and polarization, and is crucial for organism development and tissue homeostasis [2,5,6,7]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In colorectal cancer, high Wnt5a + CD68 + /CD68 + TAMs ratio is linked to poor prognosis. Wnt5a induces macrophages to secrete IL-10 via the CaKMII-ERK1/2-STAT3 pathway, promoting M2 polarization of tumor-associated macrophages (TAMs), which in turn promotes CRC cells proliferation, migration, and invasion [1]. In breast cancer, WNT5A knockdown in HB2 mammary epithelial cells leads to EMT-like changes and increased invasiveness, while in breast cancer cells, WNT5A signaling inhibits migration and invasion through an EMT-independent mechanism by decreasing CD44 expression [3]. In ovarian cancer, downregulating Wnt5a expression suppresses cell migration and invasion abilities [4].

In summary, Wnt5a plays a significant role in multiple cellular processes and is involved in the development and progression of various cancers, including colorectal, breast, and ovarian cancers. The study of Wnt5a using KO/CKO mouse models has revealed its complex functions in these disease conditions, providing insights into potential therapeutic strategies targeting Wnt5a for cancer treatment.