13th Cancer Science Course

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演者：Noriko Gotoh , Division of Cancer Cell Biology, Cancer Research Institute, Kanazawa University

演題：FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters.
座長：生化学　教授　下野洋平
Abstract：
Emerging evidence indicates that cancer stem cells (CSCs) are heterogenous cell populations and maintained in the CSC niche, the tumor microenvironment surrounding CSCs. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomic analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain-containing ion transport regulator 3 (FXYD3), a component of the Na+/K+ pump. Clinically, FXYD3+ CSCs were persistent during neoadjuvant chemotherapy (NAC), hence linking them to drug-tolerant persisters (DTPs) and identifying as crucial therapeutic targets. Importantly, FXYD3+ CSCs were sensitive to senolytic Na+/K+ pump inhibitors, such as cardiac glycosides. Targeting Na+/K+ pump could be a novel strategy to eliminate CSCs to improve TNBC prognosis after NAC.

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