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Updated: Oct 6, 2025
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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HELLS Is Negatively Regulated by Wild-Type P53 in Liver Cancer by a Mechanism Involving P21 and FOXM1
Stefanie Schuller1, Jan Sieker1, Philip Riemenschneider1,2
1Institute of Pathology, University Medicine Greifswald, 17475 Greifswald, Germany.
Cancers
|January 21, 2022
Summary
The tumor suppressor P53 (TP53) regulates HELLS expression in liver cancer. P53 inactivation leads to increased HELLS, a key epigenetic regulator, promoting hepatocarcinogenesis.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- The tumor suppressor P53 (TP53) is a transcription factor regulating cellular outcomes like apoptosis and senescence.
- P53's role in chromatin remodeling and its regulation of epigenetic enzymes in hepatocarcinogenesis are not well understood.
- Helicase, lymphoid specific (HELLS) is a significant epigenetic regulator implicated in liver cancer.
Purpose of the Study:
- To investigate the regulation of HELLS by P53 in the context of liver cancer.
- To elucidate the molecular mechanism by which P53 influences HELLS expression.
- To determine the clinical relevance of the P53-HELLS axis in hepatocellular carcinoma (HCC).
Main Methods:
- In vitro experiments to study gene regulation pathways.
- Analysis of HELLS expression in murine hepatocellular carcinoma (HCC) models with different Trp53 statuses.
- Correlation analysis of HELLS and FOXM1 expression in HCC patient cohorts.
Main Results:
- Helicase, lymphoid specific (HELLS) was identified as a direct P53 repression target.
- The P53-P21 (CDKN1A)-FOXM1 pathway mediates the downregulation of HELLS.
- HELLS expression is elevated in Trp53-deficient HCC models and correlates with FOXM1 in human HCC samples.
Conclusions:
- Functional or mutational inactivation of P53 contributes to HELLS overexpression in HCC.
- This study reveals a novel mechanism of P53-mediated tumor suppression in liver cancer through regulation of the epigenetic factor HELLS.
- Targeting the P53-HELLS pathway may offer new therapeutic strategies for HCC.
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