XAV-939

Functional validation experiments show that conditional deletion of IRGM1 or pharmacological inhibition of downstream signaling using XAV-939 markedly attenuates S. salivarius-induced NET formation, indicating the requirement of this pathway in the metastatic process. Furthermore, clinical sample analyses reveal that S. salivarius is significantly enriched in the tongue coating and feces of patients with CRC and is elevated within the tumor microenvironment. Together, these findings identify IRGM1-IQGAP1-mediated Wnt5a-PI3K/AKT signaling as a mechanistic link between oral microbiota and neutrophil-driven immune responses in cancer metastasis.

Although XAV939 is a known TNKS-1 inhibitor, it demonstrated comparatively reduced efficacy across binding and stability metrics. In conclusion, this integrative computational evidence supports microbial-derived compounds as promising natural candidates for TNKS-1 inhibition, offering a new avenue for in vivo validation and structure-guided discovery of next-generation microbe-based therapeutics for colorectal cancer. The online version contains supplementary material available at 10.1007/s40203-026-00585-9.

In vitro, XAV939 suppressed β-catenin-driven aerobic glycolysis in TNBC cells, downregulating β-catenin and glycolytic proteins, reducing glycolytic activity, and impairing aggressive phenotypes (proliferation, migration, invasion, clonogenicity).ConclusionOverall, our results highlight the crucial role of β-catenin in controlling aerobic glycolysis via regulation of key glycolytic proteins, thereby positively driving the progression and metastasis of TNBCs. Additionally, our data strongly establish that XAV939 effectively inhibits glycolytic phenotype, thereby suggesting its therapeutic potential in TNBC patients.

DCAF7 is up-regulated in various tumours and correlates with poor prognosis, particularly in LIHC. High DCAF7 expression is linked to CD4+ T cell infiltration, up-regulation of immune checkpoint genes and increased tumour mutational burden, suggesting a role in tumour immune escape. DCAF7 stabilises β-catenin by enhancing GSK-3β Ser9 phosphorylation, thereby driving c-Myc/cyclin D1 expression and contributing to proliferation and migration in LIHC. DCAF7-high tumours demonstrate therapeutic vulnerability to 17-AAG, docetaxel and CDK/GSK-3 inhibitor, revealing potential targeted treatment strategies.

Co-treatment with the tankyrase inhibitor XAV-939 and RSL3 enhanced growth inhibition of eCCA cells, indicating that WNT signaling contributed to ferroptosis resistance. These findings indicate that iCCA exhibits a preferential dependency on GPX4, whereas WNT-β-catenin signaling mediates resistance in eCCA. Collectively, the results clarify the molecular basis of subtype-specific ferroptosis vulnerability and offer a rationale for combinatorial therapeutic strategies that integrate GPX4 and WNT pathway inhibition when treating refractory eCCA.

High YEATS2 expression activates Wnt/β-catenin signaling to promote EMT in GC and is correlated with poor prognosis of GC patients.

KDM1A regulates CRC progression by modulating epithelial-mesenchymal transition (EMT), metabolism, and Wnt signaling. Targeting KDM1A with GSK2879552 represents a promising therapeutic strategy for CRC treatment.

Importantly, treatment with XAV-939, a specific Wnt/β-catenin pathway inhibitor, abrogated the pro-oncogenic effects of SAMD4B overexpression, including Wnt/β-catenin pathway activation, enhanced proliferation, and increased metastatic capacity...In summary, our findings clarify that SAMD4B exerts an oncogenic role in breast cancer progression by activating the Wnt/β-catenin pathway. These data identify SAMD4B as a potential therapeutic target in breast cancer, although further in vivo investigations are required to validate its clinical relevance.

Pharmacological interventions using Wnt3a (activation) and XAV939 (inhibition) modulated Wnt/β-catenin signaling, while CRISPR/Cas9-mediated RelB knockout and plasmid-based overexpression established isogenic cell models...This plant-derived alkaloid exerts anti-HCC effects through Wnt pathway modulation, while compensatory RelB activation constrains therapeutic outcomes. Strategic RelB co-targeting establishes a dual pathway phytotherapy paradigm, synergistically merging botanical pharmacodynamics with precision oncology.

Functional rescue experiments confirmed that BGN overexpression reverses the inhibitory effects of GLIS2 knockdown, while the Wnt/β-catenin inhibitor XAV-939 effectively blocks BGN's tumor-promoting effects. These findings establish the crucial role of the GLIS2-BGN-Wnt/β-catenin axis in regulating GC EMT and identify novel potential therapeutic targets for GC treatment.

Our results indicate that the DJQ decoction suppresses tumor progression by inhibiting the Wnt/β-catenin pathway, offering a promising treatment approach for MM.

Notably, we found that supplementing the mTeSR1 basal medium with XAV939, a Wnt/β-catenin pathway inhibitor, supported robust self-renewal and pluripotency maintenance of SD-iPSCs. Furthermore, using a bovine trophoblast stem cells (TSC) induction protocol, we successfully derived CDX2-positive trophoblast-like cells from SD-iPSCs. The establishment of SD-iPSCs not only offers a valuable model for studying mammalian pluripotent stem cells but also provides a versatile platform for biotechnological and translational research.