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Updated: Jul 2, 2025
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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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Exploring the Functions of Mutant p53 through TP53 Knockout in HaCaT Keratinocytes
Daniil Romashin1, Alexander Rusanov1, Viktoriia Arzumanian1
1Institute of Biomedical Chemistry, Moscow 119121, Russia.
Current Issues in Molecular Biology
|February 23, 2024
Summary
Mutant TP53 (tumor protein p53) in HaCaT cells drives oncogenic properties, suppressing differentiation but promoting migration and invasion. Complete TP53 knockout revealed its unexpected oncosuppressive roles.
Area of Science:
- Cancer Biology
- Molecular Oncology
- Cellular Transformation
Background:
- TP53 mutations are common in human cancers, impacting tumor progression.
- HaCaT keratinocytes, despite normal classification, harbor gain-of-function TP53 mutations.
- Understanding mutant p53 function is key to deciphering cancer mechanisms.
Purpose of the Study:
- To investigate the functional roles of mutant p53 in HaCaT cells.
- To analyze the effects of complete TP53 abolishment on cellular behavior and gene expression.
- To explore the potential oncosuppressive functions of p53.
Main Methods:
- Transcriptomic and proteomic profiling were utilized.
- CRISPR-mediated TP53 knockout was performed in HaCaT cells.
- Analysis of gene expression related to invasion, migration, EMT, and differentiation.
Main Results:
- TP53 knockout induced significant transcriptomic and proteomic alterations.
- Cell migration rate increased, and genes linked to invasion, migration, and EMT were upregulated.
- The epidermal differentiation program was suppressed following TP53 knockout.
Conclusions:
- Dysfunctional p53 may retain oncosuppressive functions.
- HaCaT cells exhibit oncogenic characteristics despite their normal keratinocyte classification.
- TP53 status critically influences keratinocyte behavior and oncogenic potential.
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