EMT-ciliary signaling in quasi-mesenchymal stem-like cells mediates TNBC therapeutic resistance

ABSTRACT: 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 suf

SUBMITTER: Camille, E Tessier 

PROVIDER: S-SCDT-10_1038-S44321-025-00289-1 | biostudies-other |

REPOSITORIES: biostudies-other