XAV-939

It was confirmed that HPOE had a certain inhibitory effect on the activation of the Wnt signaling pathway caused by the activator Licl and could enhance the inhibitory effect of the inhibitor XAV939. Our findings provide a basis for developing functional foods or dietary supplements, especially positioning HPOE as a functional food raw material for adjuvant treatment of CRC, given its ability to inhibit metastasis through the Wnt/β-catenin pathway.

Our finding demonstrate that single knockdown of Dsg2 or Dsc2 could promote proliferation, motility and invasion in triple-negative MDA-MB-231 and luminal MCF-7 cells. Nevertheless, the underlying mechanisms were cellular context-specific and distinct.

Furthermore we found that continued exposure to XAV, further addition of neither liraglutide nor insulin-like growth factor-1 counteracted XAV-mediated inhibition of IK(erg). Overall the suppression of IK(erg) by XAV may serve as a significant ionic mechanism that contribute to the functional properties of MA-10 cells. However, it is important to note that this effect cannot be attributed solely to the inhibition of tankyrase.

The tankyrase inhibitor XAV939, effectively prevents RNF166-dependent destabilization of angiomotins and subsequent activation of YAP...Importantly, the C-terminus of RNF66, particularly the Di19-ZF domain, is the crucial region responsible for recognizing ADP-ribosylated angiomotins. Together, this work not only sheds light on the regulation of the Hippo pathway in colorectal cancer but also uncovers a novel poly(ADP-ribose)-binding domain, which may serve as a potential therapeutic target for intervention.

In this study, novel reprogrammed pluripotent stem cells (rPSCs) were induced from mouse EpiSCs using a chemically defined medium containing mouse LIF, BMP4, CHIR99021, XAV939, and SB203580...Conversely, overexpression of pri-miR-290 reversed these changes. In addition, Map2k6 was identified as a direct target gene of miR-291b-3p, indicating that the miR-290 family maintains pluripotency and self-renewal in rPSCs by regulating the MAPK signaling pathway.

XAV-939, Fulvestrant, and SR16157 may have potential value in the clinical use of LUAD. We revealed the potential linkage between PRGs and LUAD prognosis, and the application of these prognostic factors in risk stratification and prognosis prediction of LUAD patients may be of great significance.

Meanwhile, further studies showed that in SW48 cells, overexpressing SLC26A9 was cocultured with the β-catenin inhibitor XAV-939, β-catenin was downregulated, and EMT was reversed. Our study demonstrated SLC26A9 may be responsible for alterations in the proliferative ability and aggressive potential of CRC by regulating the Wnt/β-catenin signaling pathway.

BIRC6 was also upregulated in cancer stem-like cells of RCC and increased the drug resistance of RCC cells against sunitinib...Pharmacological administration of a Wnt/β-catenin inhibitor, XAV-939, or genetic knockdown of β-catenin inhibited cell growth, tumor sphere formation, colony formation, migration, and invasion of BIRC6-overexpressed cells...In conclusion, we propose that BIRC6 activates the β-catenin signaling pathway via mediating the ubiquitination and degradation of Axin, promoting the growth, stemness, and drug resistance of RCC cells. This project aims to elucidate the role of BIRC6 as a potential therapeutic target and provide new insights into the clinical treatment of RCC.

Consistent with this notion, β-catenin inhibition using XAV939 or ICG-001 partially prevented centrinone-induced death and rescued the growth two APC-mutant organoid lines tested. Our study reveals a novel role for canonical WNT signaling in regulating centrosome loss-induced growth defect/death in a subset of APC-mutant colorectal cancer independently of the classical p53 pathway.

Targeting the LASS2 and β-catenin pathways may be an effective strategy to overcome cisplatin resistance and inhibit tumor growth in bladder cancer patients.

PRRX1 is upregulated in oesophageal cancer is closely correlated with cancer metastasis. Additionally, PRRX1 induces EMT in oesophageal cancer metastasis through activation of Wnt/β-catenin signalling.

The enhancing effects of FAM83F overexpression on CC cell proliferation and glycolysis could be impaired by the Wnt/β-catenin inhibitor XAV939...In summary, our study demonstrated that FAM83F promoted CC growth and glycolysis through regulating the Wnt/β-catenin pathway, suggesting that FAM83F may be a potential molecular target for CC treatment. Schematic summary of c-Myc-activated FAM83F transcription to promote cervical cancer growth and glycolysis by targeting the Wnt/β-catenin signal pathway.

The Wnt/β-catenin pathway inhibitor, XAV939, prevents the adhesion and survival of POU5F1-expressing cells in vitro. Early administration of XAV939 also completely inhibits liver metastasis induced by POU5F1-positive cells.

These findings suggest that TBX3 may play an important role in the development of ADM. The expression of TBX3 in ADM was regulated by the Wnt3a/β-catenin pathway. The activation of the Wnt3a/β-catenin pathway in ADM promoted TBX3 expression and induced the occurrence of EMT, thus promoting cell proliferation and inhibiting apoptosis, ultimately accelerating the development of ADM. The study provides a reference for the diagnosis of ADM.

GOLPH3 promotes cell proliferation, migration and invasion in CC, possibly by regulating the Wnt/β-catenin signaling pathway, which may provide a new idea for the development of CC therapeutic targets.

The β-catenin inhibitor XAV939 significantly downregulated autophagy, whereas the activator LiCl showed opposite effects. Chloroquine inhibited these phenomena, but did not completely attenuate the effects of H. pylori. These results demonstrate that chloroquine can be used as a drug for the treatment of H. pylori-related gastric cancer, but the treatment should simultaneously remove H. pylori infection.

The triple mutation status may serve as a negative prognostic and predictive factor across treatments compared to KRAS-only. KRAS G12C generally seems to be a negative predictive marker for ICI-therapy.

However, XAV-939 treatment blocked ECM accumulation and NASH-driven HCC in FGF9 mice fed with HFHC diet. Molecular mechanism studies show that FGF9 stimulated the expression of ECM related genes in a β-catenin dependent manner; and FGF9 exerts its effect on β-catenin stability via the ERK1/2-GSK-3β signaling pathway. In summary, the data provides evidence for the critical role of FGF9 in NASH-driven HCC pathogenesis; wherein it promotes the tumors formation through the ECM pathway.

Two CRC cell lines, COLO205 and DLD1, were treated with cryptolepine or XAV 939 (a WNT inhibitor) in the presence or absence of WNT3a (a WNT activator)...Altogether, cryptolepine suppresses CRC cell proliferation, stemness, and metastatic properties by inhibiting WNT3a-mediated activation of the WNT/β-catenin signaling pathway. These findings provide a rationale for considering cryptolepine as a potential WNT inhibitor in CRC.

XAV939, the Wnt/β-catenin pathway inhibitor, partly abolished the biological behaviors mediated by PARG overexpression. In conclusion, PARG promoted the malignant advancement of EC via activating the Wnt/β-catenin pathway. These findings suggested that PARG might be a new therapeutic target for EC.

The administration of the β-catenin inhibitor XAV-939 abolished the promotion of cell proliferation, migration, and invasion activities induced by ARPC1B overexpression in vitro. ARPC1B was overexpressed in ovarian cancer and was correlated with poor prognosis. ARPC1B promoted ovarian cancer progression through activation of Wnt/β-catenin Signaling Pathway.

Furthermore, our results showed that the Wnt/β-catenin pathway was inhibited by its specific inhibitor XAV-939, but miR-5590-3p inhibitor and adenoviral TNIK overexpression vector (Ad-TNIK) reactivated the activation of Wnt/β-catenin signaling and increased cell malignancy. Lastly, tumorigenicity assay demonstrated that inhibition of miR-5590-3p increased tumor volume and weight in vivo. In conclusion, miR-5590-3p may function as a cancer suppressor gene in OC progression through the Wnt/β-catenin signaling by transcriptionally suppressing TNIK expression, which provides a potential therapeutic approach for ovarian cancer treatment.

Furthermore, inhibition of Wnt/β-catenin signaling, following cell treatment with XAV-939, an inhibitor of the Wnt/β-catenin signaling pathway, abrogated the effects of CRP-1 on enhancing the proliferation and migration of HCC cells. These findings indicated that the regulatory effect of CRP-1 on HCC cells could be mediated by the Wnt/β-catenin signaling pathway. Overall, CRP-1 could promote the proliferation and migration of HCC cell lines, partially via promoting EMT and activating the Wnt/β-catenin signaling pathway.

Finally, we show that local intra-tumoral delivery of XAV-Nps during conjunctival melanoma progression significantly suppresses tumor size and melanoma progression compared to Con-Nps-treated animals. Collectively, our data suggest that selective inhibition of β-catenin in tumor cells using nanoparticle-based targeted delivery represents a novel approach to suppress tumor progression through increased tumor cell ICD.

Oxaliplatin resistance was assessed using CCK‑8 and apoptosis assays in vitro, and using a tumor xenograft model in vivo...Notably, inhibition of this pathway with a specific β‑catenin inhibitor (XAV‑939) could impair the effects induced by the overexpression of FOXD1. In summary, these results indicated that FOXD1 may promote cell stemness and the chemoresistance of CRC by binding directly to β‑catenin and enhancing β‑catenin nuclear localization; therefore, it may be considered a potential clinical target.

Wnt/β-catenin signaling pathway activation was inhibited using XAV-939, and a xenograft mouse model was generated to clarify the function of TMZ in vivo. Our data reveal a novel role of UBE2T in mediating TMZ resistance of GBM cells via regulating Wnt/β-catenin signaling. These findings indicate that targeting UBE2T has promising potential to overcome TMZ resistance of GBM.

Further, using a mouse model of conjunctival melanoma, we show that β-catenin inhibition significantly suppresses conjunctival melanoma progression. Collectively, the local delivery of β-catenin represents a novel and safe approach to promoting ICD and activating anti-tumor immunity for combinatorial immune checkpoint inhibition therapies against vision and life-threatening ocular melanomas.

Similarly, XAV939 nanoparticle treatment of macrophages in co-culture conditions resulted in significantly increased TNF-α and IL-6 and reduced IL-10 production by macrophages compared to control groups. Our data suggest that targeted inhibition of β-catenin in tumor associated macrophages could overcome tolerance and promote anti-tumor immunity.

HuH-6 and HepG2 cells were subjected to assays of cellular activities after treatment with sh-KDM1A, sh-DKK3, and/or XAV-939 (an inhibitor of the Wnt/β-catenin pathway)...Knockdown of KDM1A reduced the tumor mass, inactivated the Wnt/β-catenin signaling, and increased the expression of DKK3 in nude mice. KDM1A stimulates HB development by activating the Wnt/β-catenin pathway through inhibition of DKK3 transcription.

Our results have revealed that miR-138-5p/MeCP2/Wnt/β-catenin signaling might be a new target axis for glioma treatment strategies.

Our PDC models recapitulated the molecular characteristics of lung cancer, and pharmacogenomics analysis provided plausible therapeutic candidates.

However, XAV939 inhibited STMN2 overexpression-enhanced EMT and proliferation...STMN2 overexpression promotes the aggressive clinical stage of PC patients and promotes EMT and cell proliferation in vitro and vivo. β-catenin/TCF-mediated the transcription of STMN2.

In addition, the β-catenin inhibitor XAV-939 significantly attenuated the upregulation of the aforementioned proteins and inhibited the increased migration and invasion caused by the H3.3K27M mutation. Overall, the H3.3K27M mutation in high-grade glioma is a potential biomarker for poor prognosis mainly due to the infiltration of glioma cells that is at least partially mediated by the β-catenin/USP1/EZH2 pathway.

Taken together, the findings of our research highlight a novel role for fucoxanthin in NSCLC cells, which might be a potentially effective anti-tumor agent for the treatment of LUAD patients.

Arylsulfatase I is a promising prognostic and therapeutic target for HNSC.

In addition, TRIM50 knockdown-promoted cell proliferation and metastasis in GC cells were inverted by XAV939. TRIM50 overexpression may inhibit cell proliferation and metastasis in GC via β-catenin degradation, indicating that TRIM50 could be a target for the treatment of GC.

BCa cells were treated with XAV-939, LiCl and 2-deoxyglucose. SMAR1 might suppress the Wnt/β-catenin signaling pathway activity to inhibit the progression of BCa. It might be an effective treatment target for BCa.