DVL2 (Dishevelled Segment Polarity Protein 2)

Furthermore, PRICKLE3 interacted with USP9X to inhibit the DVL2 ubiquitination for the DVL2 stability and the activation of canonical WNT signaling. Overall, we demonstrate a novel signal transduction pathway where PRICKLE3 interacts with USP9X and DVL2 to enhance the DVL2 deubiquitination mediated by USP9X for stabilizing DVL2 expression and activate the canonical WNT signaling for promoting the NSCLC progression.

Additionally, the apo structure of human Dvl2PDZ shows conformational dynamics different from its IPM peptide bound state, suggesting an induced fit mechanism for the Dvl2PDZ-peptide interaction. The current study provides a model for Dvl2 induced activation of WGEF.

The MTT experiment results of the obtained neolignans on HT29 and LoVo cells indicated previously undescribed neolignans, penthoneolignans A (1) and F (6), showed better cytotoxicity than the positive drug 5-fluorouracil. Furthermore, a Western blot assay combining the Dsh homolog 2 agonist IWP-L6 and the β-catenin agonist MG132 suggested their mechanism of action was closely related to the inhibition of the Wnt/β-catenin signaling pathway. In conclusion, previously undescribed neolignans, penthoneolignans A (1) and F (6), may intervene in the development and progression of colorectal cancer by inhibiting the Wnt/β-catenin signaling pathway and have the potential to be drug candidates.

Collectively, our study revealed the important role of AQP9 in regulating DVL2 stabilization and Wnt/β-catenin signaling to promote CRC metastasis. Targeting the NEDD4L-AQP9-DVL2 axis might have therapeutic usefulness in metastatic CRC treatment.

DVL2 is highly expressed in gastric cancer tissues, which may be a new independent risk factor for the prognosis of gastric cancer patients. In gastric cancer, DVL2 overexpression plays a crucial role in the occurrence and development of gastric cancer, so it may become a new, effective and complementary therapeutic target for gastric cancer.

Moreover, the silencing of ASPM attenuated the expressions of crucial proteins involved in Wnt/b-catenin signaling pathway, including Dvl-2, β-catenin, TCF4, and LEF1. Our study shows the biological significance of ASPM in PRCC and provides new insights for exploring therapeutic targets in PRCC.

Our study demonstrates potential immune regulatory role of DVL2 proteins in HER2+ BC. More in-depth mechanistic studies of DVL paralogs and their influence on anti-tumor immunity may provide insight into DVLs as potential therapeutic targets benefiting BC patients.

Overexpression of DACT3 impeded the formation and growth of AML-derived xenograft tumor. Collectively, our work reveals a tumor-suppressive role of DACT3, a protein that negatively adjusts Wnt/β-catenin pathway via downregulation of DVL2 in AML.

Increased expression of ETV4 promotes HCC cell invasion and metastasis by upregulating DVL2. The present study provides insight into the ETV4-DVL2-β-catenin axis in HBV-related HCC, which will be helpful for treating patients with aggressive HCC.

In conclusion, the findings of the present study suggested that the Wnt signaling pathway components SFRP1, SFRP3, DVL2 and DVL3 may be aberrantly expressed in DGC tissues, implicating their possible role in the development of this malignant disease. The present data also revealed a positive relationship between SFRP3 protein expression and the clinical and T stage of DGC.