Dasatinib Inhibits Basal B Breast Cancer Through ETS1-Mediated Extracellular Matrix Remodeling

作者：Xinyu Guo, Heng Sun, Yu Feng, Yangyang Feng, Sen Guo, Josh Haipeng Lei, Kai Miao, Ka U. Ip, Ling Li, Hanghang Li, Xiaohong Liao, Xiaoling Xu, Rong Zhou, Chu‐Xia Deng · 发表于：Biomedicines · 年份：2025 · DOI：10.3390/biomedicines13122888 · 被引用次数：2 · 研究领域：Cancer Cells and Metastasis、Cancer, Stress, Anesthesia, and Immune Response、Protease and Inhibitor Mechanisms

Background/Objectives: Developing effective therapies for patients with triple-negative breast cancer (TNBC) remains an urgent clinical priority. Compared with other subtypes, the basal B type of TNBC exhibits a less differentiated and mesenchymal-like phenotype that models highly invasive and metastatic breast malignancies. To target metastatic TNBC, our current study sought to identify effective therapeutic drugs and the underlying mechanisms. Methods: A systematic screening of 140 FDA-approved drugs was conducted for repurposing using live-cell imaging-based wound-healing assays. Candidate efficacy was validated by in vitro transwell invasion assays, in vivo allograft/xenograft models, and ex vivo three-dimensional air–liquid interface (ALI) and patient-derived organoid (PDO) cultures. Results: Dasatinib emerged as a promising anti-cancer agent in aggressive TNBC, particularly in the basal B type, with high ETS proto-oncogene 1 (ETS1) expression. Mechanistically, dasatinib disrupts the actin cytoskeleton, impairing cell motility and migration while concurrently suppressing the expression of ETS1 and matrix metalloproteinase-3 (MMP3) to remodel the extracellular matrix (ECM) and inhibit invasion. Moreover, the combination of dasatinib with an anti-programmed cell death protein-1 (PD-1) antibody represents a potential therapeutic strategy. Conclusions: These findings highlight dasatinib as a potential therapeutic option for metastatic TNBC and suggest that selecting patients...