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Updated: Jun 12, 2025

A Two-Step Strategy that Combines Epigenetic Modification and Biomechanical Cues to Generate Mammalian Pluripotent Cells
Published on: August 29, 2020
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.
Abstract:
The intricate interplay of cancer stem cell plasticity, along with the bidirectional transformation between epithelial-mesenchymal states, introduces further intricacy to offer insights into newer therapeutic approaches. Differentiation therapy, while successful in targeting leukemic stem cells, has shown limited overall success, with only a few promising instances. Using colon carcinoma cell strains with sequential p53/p73 knockdowns, our study underscores the association between p53/p73 and the maintenance of cellular plasticity. Morphological alterations corresponding with cell surface marker expressions, transcriptome analysis and functional assays were performed to access stemness and EMT (Epithelial-Mesenchymal Transition) characteristics in the spectrum of cells exhibiting sequential p53 and p73 knockdowns. Notably, our investigation explores the effectiveness of esculetin in reversing the shift from an epithelial to a mesenchymal phenotype, characterized by stem cell-like traits. Esculetin significantly induces enterocyte differentiation and promotes epithelial cell polarity by altering Wnt axes in Cancer Stem Cell-like cells characterized by high mesenchymal features. These results align with our previous findings in leukemic blast cells, establishing esculetin as an effective differentiating agent in both Acute Myeloid Leukemia (AML) and solid tumor cells.
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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