BRCA1 as a target for attenuating paclitaxel resistance by Halofuginone treatment in basal-like breast cancer

Abstract

Breast cancer presents significant challenges in oncology, particularly basal-like breast cancer (BLBC), which shows resistance to paclitaxel treatment. This study examines the efficacy of halofuginone (HF), a compound from traditional Chinese medicine, in mitigating this resistance by targeting the BRCA1/TGF-β signaling axis affecting epithelial-mesenchymal transition (EMT). Using analyses such as weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) enrichment from TCGA database RNA-seq data, along with transcriptomic sequencing and in vitro experiments, our findings demonstrate HF’s ability to modulate BRCA1 expression, impacting cell migration, invasion, and EMT in resistant BLBC cells. BRCA1 knockout experiments further reveal that HF’s effects on EMT can be reversed, underscoring the crucial role of the BRCA1-TGFBR2 axis in drug resistance. This study sheds light on HF’s mechanism in overcoming paclitaxel resistance and suggests new treatment avenues for BLBC, showcasing the potential integration of traditional Chinese medicine in modern therapeutic strategies.

Keywords

• Halofuginone
• Paclitaxel resistance
• Basal-like breast cancer
• Traditional Chinese medicine
• Epithelial-mesenchymal transition
• BRCA1