Work

The tumor suppressor DACT3 sensitizes triple-negative breast cancer to apatinib by inhibiting the Wnt/β-catenin pathway

Year: 2025

Type: article

Abstract: Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), shows efficient antitumor activity in heavily pretreated metastatic triple-negative breast cancer (TNBC). However, not all patients respond to apatinib, indicating that it is necessary to identify response biomarkers for more precise treatment and investigate the underlying mechanisms of apatinib resistance to develop new treatment strategies for TNBC. In this study, we identified the disheveled binding antagonist of beta-catenin 3 (DACT3) as a biomarker for apatinib sensitivity, as its expression level is significantly higher in apatinib-sensitive patients and positively correlates with longer survival. Furthermore, we explored that the exogenous expression of DACT3 could downregulate the IC 50 of apatinib (Vector vs DACT3: 16.04 μM vs 8.81 μM in MDA-MB231 cells, 19.65 μM vs 9.42 μM in YCCB1 cells) by inhibiting the Wnt/β-catenin signaling, a pro-malignancy pathway that leads to apatinib resistance through crosstalk with the VEGF/VEGFR2 pathway. In summary, our results indicate that DACT3 is a potential biomarker for predicting the response to apatinib and a new therapeutic target for improving TNBC sensitivity to apatinib.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2025.102509

Authors: Jing Wu, Rui Tian, Mei Liu, Yijing Liu, Bianfei Shao, Xiaohua Zeng

Institutions: Chongqing University, Chongqing Cancer Hospital

Language: English

Topic: Wnt/β-catenin signaling in development and cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,390