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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs
Chun-Ju Chang1, Chi-Hong Chao, Weiya Xia
1Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Nature Cell Biology
|February 22, 2011
Summary
Tumor suppressor p53 activates miR-200c, regulating the epithelial-mesenchymal transition (EMT) and stemness. Loss of p53 decreases miR-200c, promoting EMT and cancer stem cells, highlighting a therapeutic target.
Area of Science:
- Molecular Biology
- Cancer Research
- Stem Cell Biology
Background:
- The epithelial-mesenchymal transition (EMT) is linked to stem cell phenotypes, but underlying mechanisms remain unclear.
- Understanding the regulation of EMT and stemness is crucial for cancer research.
Purpose of the Study:
- To investigate the role of tumor suppressor p53 in regulating EMT and stemness.
- To elucidate the molecular mechanism connecting p53, miR-200c, EMT, and stem cell properties.
Main Methods:
- Genomic approaches were employed to study gene regulation.
- Direct binding of p53 to the miR-200c promoter was assessed.
- Expression levels of p53, miR-200c, EMT markers, and stemness markers were analyzed in cell lines and patient tumors.
Main Results:
- p53 directly activates the transcription of microRNA miR-200c.
- Loss of p53 in mammary cells decreases miR-200c, activating EMT and increasing stem cell populations.
- Re-expression of miR-200c suppresses EMT and stemness, reverting cells to an epithelial phenotype.
- In breast tumors, p53 loss correlates with decreased miR-200c, increased EMT/stemness markers, and higher tumor grade.
Conclusions:
- p53 plays a critical role in regulating the balance between EMT and MET (mesenchymal-epithelial transition), influencing stemness and differentiation plasticity.
- The p53-miR-200c pathway represents a potential therapeutic target for suppressing EMT-associated cancer stem cells.
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