USP7 regulates growth and maintains the stemness of p53-mutant colorectal cancer cells via stabilizing of mutant p53
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View abstract on PubMed
Summary
This summary is machine-generated.USP7 stabilizes mutant p53, promoting colorectal cancer stem cell growth and migration. Inhibiting USP7 reduces cancer cell proliferation and stemness, offering a potential therapeutic strategy for TP53-mutated colorectal cancers.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background
- TP53 mutations are prevalent in colorectal cancers (CRCs), occurring in over 40% of cases.
- Accumulated mutant p53 protein can enhance colorectal cancer stem cell (CCSC) phenotypes and promote tumor development.
- Targeting mutant p53 levels presents a promising anticancer strategy.
Purpose Of The Study
- To investigate the role of USP7 in the regulation of colorectal cancer stem cells (CCSCs).
- To determine if USP7 modulates mutant p53 protein levels and affects CCSC properties.
- To evaluate USP7 as a potential therapeutic target in colorectal cancer.
Main Methods
- Tumor sphere formation assays to enrich for cancer stem cells.
- Cell proliferation (MTS, colony formation), migration (wound healing), and stemness assays.
- Gene expression and protein level analysis (qPCR, Western blotting, co-immunoprecipitation) for USP7, p53, and CSC markers.
- Treatment with USP7 inhibitor P5091.
Main Results
- USP7 and mutant p53 were significantly elevated in CCSC-enriched cells.
- USP7 expression correlated positively with CCSC self-renewal and maintenance.
- USP7 depletion reduced cancer cell proliferation, migration, and CCSC self-renewal.
- USP7 knockdown decreased mutant p53 protein levels, indicating USP7 stabilizes mutant p53.
- USP7 and mutant p53 interact, and USP7 inhibition reduced CCSC self-renewal and mutant p53 levels.
Conclusions
- USP7 plays a crucial role in modulating CCSC stemness and tumorigenesis.
- USP7 stabilizes mutant p53, contributing to colorectal cancer progression.
- USP7 inhibition demonstrates therapeutic potential for colorectal cancers with p53 mutations.
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