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EMT-ciliary signaling in quasi-mesenchymal-stem-like cells drives therapeutic resistance and is a druggable vulnerability in triple-negative breast cancer

GSE298840 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/06/30 Platform GPL24676
Summary
Cancer therapeutic resistance is mediated, in part, by phenotypic heterogeneity and the plasticity of tumor cells, the latter being enabled by Epithelial-Mesenchymal Transition (EMT). However, EMT in human cancer therapeutic response remain poorly understood. We developed patient-derived organoids (PDOs) from human triple-negative breast cancer (TNBC) and investigated their response to chemotherapy. We found that chemotherapy treatment kills the bulk of tumor cells in PDOs, but there is selective survival of malignant cells that had activated an EMT program, entered a quasi-mesenchymal, stem cell-like state and display primary cilia. We developed a family of small-molecule inhibitors of ciliogenesis and show that treatment with these inhibitors, or genetic ablation of primary cilia, is sufficient to suppress this chemoresistance via NFB-induced cell death. We conclude that an EMT-ciliary signaling axis induces chemoresistance in quasi-mesenchymal stem-like cells to help tumors evade chemotherapy and represents a druggable vulnerability in human TNBC.
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EMT-ciliary signaling in quasi-mesenchymal-stem-like cells drives therapeutic resistance and is a druggable vulnerability in triple-negative breast cancer
Tessier CE, Derrien J, Dupuy AMM et al. · EMBO molecular medicine 2025 · PMID 40859055 · doi:10.1038/s44321-025-00289-1
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Also filed as BioProject PRJNA1271467 and SRA study SRP589572. Searching any of these in the dataset finder brings you back here.

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