Wnt/β-catenin pathway
Wnt/β-catenin pathway
Overview
The Wnt/β-catenin pathway is a conserved cell-signaling cascade that regulates embryonic development, tissue homeostasis, stem cell behavior, and cell fate decisions. In the canonical pathway, Wnt ligand stimulation stabilizes β-catenin, allowing it to accumulate and translocate to the nucleus, where it cooperates with transcriptional regulators such as TCF4 to drive expression of target genes including CCND1 and MYC. When the pathway is not appropriately controlled, β-catenin signaling can become aberrantly activated and contribute to tumorigenesis, altered differentiation, fibrosis, and other disease processes.
In biomedical research, the pathway is frequently studied as both a mechanistic node and a therapeutic target. Recent studies in colorectal cancer, lung adenocarcinoma, breast cancer, skeletal aging, and fibrosis-associated models have examined how modulation of Wnt/β-catenin signaling intersects with inflammatory signaling, oxidative stress, ferroptosis, ER stress, ciliogenesis, and drug resistance. The pathway is also relevant in bone biology, where WNT signaling supports bone health and inhibitors such as Sclerostin can influence skeletal deterioration.
Focus of Latest Publications
Recent publications have continued to position the Wnt/β-catenin pathway as a recurring mechanistic node across diverse disease models, especially in cancer, bone biology, metabolic disease, and tissue repair. Several studies used multi-omics, transcriptomics, proteomics, single-cell RNA sequencing, or mechanistic cell and animal experiments to link pathway activity to therapeutic responses. In spinal cord injury, electroacupuncture was reported to restore DHCR24 expression and promote recovery by attenuating neuronal apoptosis and neuroinflammation, with the authors proposing that these effects were mediated through Wnt signaling activation. In critical-sized bone defect repair, a magnesium-loaded biomimetic scaffold recruited a CCN3+ mesenchymal stem cell subpopulation that participated in early osteogenesis via Wnt/β-catenin signaling. In skeletal aging, microRNA profiling identified WNT-pathway-associated miRNAs, including miR-183-5p, and the study further examined how sclerostin neutralization influenced WNT- and senescence-related gene programs.
In oncology, the pathway was repeatedly implicated in tumor growth, survival, and drug resistance. In hepatocellular carcinoma, F9 was described as a tumor suppressor that interacts with SERPINC1 to inhibit Wnt/β-catenin signaling. In breast cancer, nuclear XIAP overexpression was associated with altered expression of Wnt/β-catenin-related genes and activation of β-catenin transcriptional activity, with IGFBP6 emerging as a potential regulatory node. In colorectal cancer, dual targeting of TROP2 and PERK was reported to suppress the Wnt/β-catenin pathway and overcome resistance to an antibody-drug conjugate, while an 8-sulfonamidoquinoline derivative was suggested to inhibit WNT/β-catenin signaling by binding P65. A separate study identified Basroparib (STP1002) as a potent and selective tankyrase inhibitor that suppresses cellular Wnt/β-catenin signaling, supporting its development for Wnt-driven cancers.
Other studies linked Wnt/β-catenin signaling to metabolic and differentiation-related phenotypes. In obesity research, adzuki bean saponin and its active component soyasaponin Ba were reported to improve high-fat-diet-induced metabolic abnormalities by activating Wnt/β-catenin signaling. In osteoblastogenesis, novel ten-membered lactones were screened for bone-forming activity, and compounds 4 and 8 were identified as osteoblastogenesis agents that activate Wnt/β-catenin signaling, with compound 8 also alleviating dexamethasone-induced osteoporotic changes in zebrafish. In lung adenocarcinoma, artesunate reversed gefitinib resistance by inducing ferroptosis and suppressing Wnt/β-catenin signaling, accompanied by changes in GSK3β, β-catenin, TCF4, Cyclin D1, and c-MYC. Collectively, these publications reinforce the pathway’s broad relevance as a therapeutic target and biomarker across regenerative, inflammatory, metabolic, and malignant contexts.