Protein Wnt-5a (WNT5A) (WNT5A)

Protein Wnt-5a (WNT5A) is a highly conserved secreted glycoprotein belonging to the Wnt family, primarily functioning through non-canonical, beta-catenin-independent signaling pathways such as the Wnt/Ca2+ and planar cell polarity (PCP) pathways [1, 4]. It plays a critical role in embryonic development, regulating cell fate, patterning, and tissue morphogenesis, while in adults, it maintains tissue homeostasis and modulates immune responses [3, 5]. Wnt5a exhibits a complex, context-dependent role in human diseases, particularly cancer, where it can act as either a tumor suppressor or an oncogene by influencing cell migration and invasion [2, 6]. For instance, its downregulation is associated with metastasis in breast and colon cancers, whereas its overexpression promotes progression in melanoma and ovarian cancer [12, 14]. Therapeutic strategies targeting Wnt5a include the use of mimicking peptides like Foxy-5 to restore its anti-metastatic activity in low-expression tumors and antagonists like Box5 to inhibit its pro-invasive effects in high-expression malignancies [23, 24]. Clinical development has faced challenges, as seen in the recent termination of the NeoFox trial for Foxy-5 due to lack of efficacy, highlighting the difficulty of modulating this complex pathway [32]. Despite these setbacks, Wnt5a remains a significant target for research in oncology, inflammation, and regenerative medicine [11, 16].

Other names

WNT5AhWnt family member 5AWingless-type MMTV integration site family member 5AWnt-5aWnt5

Wnt5a mimics (e.g., Foxy-5) act as agonists to restore non-canonical signaling and inhibit metastasis in Wnt5a-low tumors, while Wnt5a antagonists (e.g., Box5) block ligand-receptor interactions to reduce invasion and inflammation in Wnt5a-high contexts [1, 23, 24].