Protein Wnt-2 (WNT2) (WNT2)

Protein Wnt-2 is a secreted signaling glycoprotein and a member of the Wnt family of proteins, which are essential for regulating cell fate, proliferation, and patterning during embryonic development and adult tissue homeostasis [4, 5]. It primarily functions by activating the canonical Wnt/beta-catenin signaling pathway through binding to Frizzled receptors (such as FZD9) and LRP5/6 co-receptors, leading to the stabilization and nuclear translocation of beta-catenin [3, 9]. In various malignancies, such as colorectal, non-small cell lung, and esophageal cancers, Wnt-2 is frequently overexpressed and acts as an oncogenic driver by promoting tumor cell survival, metastasis, and an immunosuppressive tumor microenvironment [6, 9, 20]. Specifically, cancer-associated fibroblast-secreted Wnt-2 has been shown to inhibit dendritic cell-mediated antitumor immunity [6, 11]. Therapeutic efforts are focused on neutralizing Wnt-2 with monoclonal antibodies or inhibiting its secretion using porcupine (PORCN) inhibitors, although the widespread physiological importance of Wnt signaling poses significant challenges regarding on-target toxicities like bone loss and gastrointestinal distress [2, 8, 16]. Additionally, Wnt-2 expression in the hippocampus has been linked to the therapeutic effects of antidepressants, suggesting a role in neuroplasticity [7].

Other names

IRPINT1L1Wingless-type MMTV integration site family member 2Secreted growth factorInt-1-related proteinWNT2

Ligand neutralization, inhibition of ligand secretion, and induction of ligand expression.