Wnt signaling pathway: Therapeutic target of natural products for cancer therapy.

The Wnt signaling pathway is an evolutionarily conserved system crucial for embryonic development, tissue homeostasis and various diseases. Wnt signaling is generally categorized into two main branches: the canonical (β-catenin-dependent) pathway and the non-canonical (β-catenin-independent) pathway, including the Wnt/planar cell polarity (PCP) and Wnt/Ca2+ pathways. The dysregulated Wnt signaling pathway is highly associated with the pathogenesis of multiple cancers, such as proliferation, apoptosis, autophagy, metastasis, immune evasion, drug resistance and maintenance of cancer stem cells. Mounting evidence reveals that natural products can effectively modulate Wnt signaling pathway through complex mechanisms, showcasing promising anticancer potency. This review systematically summarizes the transduction of Wnt signaling pathway and its intricate role in cancer, the influences of various natural products on Wnt signaling cascade, with a focus on the current understanding of their action mechanisms in cancer therapy. This review also explores the pharmacokinetics, safety and clinical trials of these natural products targeting Wnt signaling pathway in cancer, and the crosstalk between Wnt and other signaling pathways regulated by natural products in cancer, highlighting their potential as innovative therapeutic strategies for cancer treatment.