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.

Key Publications

• NEWJul Electroacupuncture-modulated DHCR24 facilitates spinal cord injury recovery by attenuating apoptosis and neuroinflammation via the Wnt signaling pathway. (Metabolic brain disease, 2026, PMID 42390651): "with a particular focus on its effects on the Wnt signaling pathway."
• Jun Anti-obesity mechanisms of adzuki bean saponin: a multi-omics and experimental study. (NPJ science of food, 2026, PMID 42248912): "The results of transcriptomics, proteomics, and immunohistochemistry indicated that ABS could achieve anti-obesity effects through activating the Wnt/β-catenin signaling pathway."
• Jun Comprehensive multi-omics analysis identifies cancer subtypes and prognostic signatures of hepatitis B virus-associated hepatocellular carcinoma. (NPJ precision oncology, 2026, PMID 42243437): "Mechanistically, we discovered that F9 acts as a tumor suppressor by interacting with SERPINC1 to inhibit the Wnt/β-catenin signaling pathway."
• Jun Flowerbed-Inspired Mg-Loaded Scaffold Accelerates Critical-Sized Bone-Defect Repair by Reprogramming the Microenvironment. (ACS nano, 2026, PMID 42204979): "which exhibited high stemness and participated in early osteogenesis via the Wnt/β-catenin signaling pathway."
• May MicroRNA networks associated with skeletal aging and WNT pathway modulation. (Calcified tissue international, 2026, PMID 42183846): "The WNT-pathway has been positively associated with bone health and Sclerostin, a WNT-pathway inhibitor produced and secreted by osteocytes, has been implicated in accelerated skeletal deterioration following radiation."
• May Cross-Organ Toxicity and Metabolic Responses to Food Chain-Transferred Nanoplastics: Mechanistic Insights from a Multiomics Perspective. (ACS nano, 2026, PMID 42103696): "Mechanistically, dysregulation of key genes, such as MTOR and FN1, activated Wnt and TGF-β signaling pathways, which in turn promoted organ fibrosis."
• Jun Transcriptomic alterations upon nuclear XIAP overexpression reveal IGFBP6/Wnt as a regulatory axis in breast cancer cell survival and chemoresistance. (European journal of pharmacology, 2026, PMID 42069172): "Interestingly, the validation analysis has shown differential expression of genes associated with the Wingless-related integration site (Wnt)/β-catenin pathway, as well as the insulin-like growth factor-binding protein 6 (IGFBP6) tumor suppressor gene."
• May PRDX4 Potentially Serves as an Independent Marker for Early Recurrence of Oral Squamous Cell Carcinoma. (Anticancer research, 2026, PMID 42049339): "Furthermore, recent studies have revealed that PRDX4 promotes tumor development through the Wnt/β-catenin signaling pathway."
• May Overcoming ADC resistance in advanced colorectal cancer by dual targeting of TROP2 and PERK to suppress Wnt/β-catenin signaling. (Cell reports. Medicine, 2026, PMID 42030933): "Mechanistically, this synergy stems from the enhanced suppression of ER stress and the oncogenic Wnt/β-catenin pathway."
• Apr Artesunate reverses gefitinib resistance in lung adenocarcinoma by inducing ferroptosis and suppressing the Wnt/β-catenin pathway. (European journal of pharmacology, 2026, PMID 41967624): "Mechanistically, ART was found to inhibit the Wnt/β-catenin pathway by upregulating GSK3β and p-β-catenin expression while downregulating β-catenin, TCF4, Cyclin D1 and c-Myc expression, thereby promoting ferroptosis."