Targeting cellular plasticity: esculetin-driven reversion of stem cell-like characteristics and EMT phenotype in

Ankit Mathur1,2, Chanchal Bareja2, Milky Mittal2

  • 1Delhi School of Public Health, Institution of Eminence, University of Delhi, Delhi, 110007, India.

BMC Cancer
|September 19, 2024
PubMed

Insights

This study reveals p53/p73

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Cancer stem cell (CSC) plasticity and epithelial-mesenchymal transition (EMT) complicate therapeutic strategies.
  • Differentiation therapy shows promise but has limited success in solid tumors.

Purpose of the Study:

  • To investigate the role of p53/p73 in maintaining CSC plasticity and EMT.
  • To evaluate esculetin's potential to reverse mesenchymal phenotypes and induce differentiation in CSCs.

Main Methods:

  • Utilized colon carcinoma cell lines with sequential p53/p73 knockdowns.
  • Performed morphological, cell surface marker, transcriptome, and functional analyses.
  • Assessed stemness and EMT characteristics.

Main Results:

  • p53/p73 are associated with the maintenance of cellular plasticity.
  • Esculetin reversed the epithelial-to-mesenchymal transition in CSC-like cells.
  • Esculetin induced enterocyte differentiation and epithelial polarity by modulating Wnt signaling.

Conclusions:

  • Esculetin demonstrates efficacy as a differentiating agent in both Acute Myeloid Leukemia (AML) and solid tumor CSCs.
  • Targeting p53/p73 and modulating Wnt signaling are potential therapeutic avenues.

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