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  2. Fxyd3 Functionally Demarcates An Ancestral Breast Cancer Stem Cell Subpopulation With Features Of Drug-tolerant Persisters.
  1. Home
  2. Fxyd3 Functionally Demarcates An Ancestral Breast Cancer Stem Cell Subpopulation With Features Of Drug-tolerant Persisters.

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FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant

Mengjiao Li1, Tatsunori Nishimura1, Yasuto Takeuchi1,2

  • 1Division of Cancer Cell Biology, Cancer Research Institute, and.

The Journal of Clinical Investigation
|November 15, 2023

View abstract on PubMed

Summary
This summary is machine-generated.

Cancer stem cells (CSCs) in triple-negative breast cancer (TNBC) show plasticity. A specific subpopulation, FXYD3+ CSCs, drives chemoresistance and may be targeted by Na+/K+ pump inhibitors.

Keywords:
Breast cancerDrug therapyOncologyStem cells

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Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Cancer stem cells (CSCs) contribute to tumor heterogeneity and therapeutic resistance.
  • Phenotypic plasticity in CSCs fuels treatment challenges, particularly in triple-negative breast cancer (TNBC).

Purpose of the Study:

  • To identify and characterize CSC subpopulations driving phenotypic heterogeneity in TNBC.
  • To investigate the role of identified CSC subpopulations in chemoresistance and therapeutic targeting.

Main Methods:

  • Single-cell transcriptomics analysis was performed on TNBC samples.
  • Identification of specific CSC markers and subpopulations.
  • Assessment of FXYD3+ CSC persistence during neoadjuvant chemotherapy.
  • Evaluation of sensitivity to Na+/K+ pump inhibitors.

Main Results:

  • A subpopulation of CSCs, marked by FXYD3 (a Na+/K+ pump component), was identified.
  • FXYD3+ CSCs exhibit ancestral features and traits of alveolar progenitors.
  • These FXYD3+ CSCs persisted through neoadjuvant chemotherapy, acting as drug-tolerant persisters (DTPs).
  • FXYD3+ CSCs demonstrated sensitivity to cardiac glycosides, which are Na+/K+ pump inhibitors.

Conclusions:

  • FXYD3+ CSCs with ancestral features are key drivers of plasticity and chemoresistance in TNBC.
  • Targeting the Na+/K+ pump offers a potential therapeutic strategy to eliminate CSCs and improve TNBC outcomes.
  • Na+/K+ pump inhibitors may effectively target both ancestral and DTP features of CSCs.