Wnt proteins are secreted glycoproteins that contain a conserved pattern of 23‑24 cysteine residues. Wnts play critical roles in both carcinogenesis and embryonic development for a variety of organisms. Wnts bind to receptors of the Frizzled family, sometimes in conjunction with other membrane-associated proteins such as LRPs or proteoglycans. Downstream effects of Wnt signaling occur through different intracellular components, depending on which pathway is activated. Three pathways have been characterized: the canonical Wnt/ beta -catenin pathway, the Wnt/Ca2+ pathway, and the planar cell polarity (1‑2).
Wnt-5a is part of the subgroup of Wnts that are not axis-inducing in Xenopus embryos and do not transform C57MG mammary epithelial cells. This subgroup is also implicated in the Wnt/Ca2+ pathway, playing roles in cell movements and cell adhesion (3). This non-canonical Wnt pathway can inhibit canonical Wnt/ beta -catenin signaling. In Wnt-5a deficient mouse embryos, beta -catenin accumulates in the limb bud suggesting that Wnt-5a normally promotes degradation of beta -catenin (4). Likewise, in Xenopus embryos Wnt-5a antagonizes the ability of the canonical Wnt subgroup to induce a secondary axis (5). Wnt-5a is implicated in various types of cancer and has complex roles. It acts as a tumor suppressor for mammary, B-cell, colon, and uroepithelial cancer cells but is up-regulated in melanomas, where expression levels correlate with severity of metastasis (3). Furthermore, aberrant Wnt-5a signaling results in other diseases such as rheumatoid arthritis (6). Like other developmental growth factors Wnt-5a has diverse roles in development. They are too numerous to enunciate here, as functions span from early anterior-posterior development and gastrulation movements to maintaining hematopoietic stem cell population, lung morphogenesis, and limb outgrowth. Mature Wnt-5a is a 49 kDa protein that shares 99% amino acid identity in mouse, rat and human.
