AI Article Synopsis

  • Cancer stem cells (CSCs) show diversity within tumors, making it hard to target treatments effectively, especially in triple-negative breast cancer (TNBC).
  • Through single-cell transcriptomics, researchers identified a specific subpopulation of CSCs characterized by FXYD3, which is linked to drug resistance during chemotherapy.
  • Targeting the Na+/K+ pump with specific inhibitors, such as cardiac glycosides, could potentially improve treatment outcomes by eliminating these resistant CSCs, leading to better TNBC patient prognoses.

Article Abstract

The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics 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. Accordingly, FXYD3+ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3+ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3+ CSCs were sensitive to senolytic Na+/K+ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3+ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na+/K+ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10645391PMC
http://dx.doi.org/10.1172/JCI166666DOI Listing

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