Wnt/Ca²⁺ signaling: Dichotomous roles in regulating tumor progress (Review)

The Wnt signaling pathway is broadly categorized into two major classes: Canonical and non-canonical pathways. The canonical Wnt pathway, which is also referred to as the Wnt/β-catenin pathway, involves the nuclear translocation of β-catenin. By contrast, non-canonical Wnt pathways, including the Wnt/Ca²⁺ pathway and the Wnt/planar cell polarity pathway, function independently of β-catenin nuclear translocation. Among these non-canonical pathways, the Wnt/Ca²⁺ pathway influences cellular behavior by elevating intracellular Ca²⁺ concentrations. This pathway primarily regulates cytoskeletal remodeling, cell migration, polarity and immune responses, and serves a crucial role in cell proliferation, differentiation, embryonic development and tumorigenesis. Notably, Wnt/Ca²⁺ signaling exhibits dual functions in different tumor types, promoting tumorigenesis in certain cancers, whilst inhibiting it in others. The present review systematically summarizes research regarding the Wnt/Ca²⁺ signaling pathway, elucidates its mechanisms in cancer progression, and outlines current strategies for targeting the Wnt/Ca²⁺ signaling pathway in cancer, along with the associated challenges.