PTPN23[Thr] variant reduces susceptibility and tumorigenesis in esophageal squamous cell carcinoma through dephosphorylation of EGFR
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View abstract on PubMed
Summary
This summary is machine-generated.Genetic variants in post-translational modifications (PTMs) influence esophageal squamous cell carcinoma (ESCC) risk. A specific PTPN23 variant (rs6780013) significantly impacts ESCC susceptibility and inhibits cancer cell growth by interacting with EGFR.
Area Of Science
- Oncology
- Genetics
- Molecular Biology
Background
- Post-translational modifications (PTMs) are crucial in cancer development, including esophageal squamous cell carcinoma (ESCC).
- Understanding genetic variations in PTMs can reveal novel insights into cancer risk and progression.
Purpose Of The Study
- To comprehensively analyze PTM-related genetic variants associated with ESCC risk.
- To identify specific variants and their functional roles in ESCC pathogenesis.
Main Methods
- Utilized large-scale genome-wide and exome-wide association datasets for ESCC.
- Performed statistical analysis to identify significant PTM-related variants.
- Conducted functional investigations on identified variants, including protein binding and cell proliferation assays.
Main Results
- Significant enrichment of PTM-related variants was observed in ESCC risk loci.
- Five variants were significantly associated with ESCC risk, with rs6780013 in PTPN23 showing the highest significance (OR=0.85, P=9.77×10⁻¹⁴).
- The PTPN23[Thr] variant interacts with EGFR, modulating its phosphorylation and inhibiting ESCC cell proliferation in vitro and in vivo.
Conclusions
- PTM-related genetic variants play a critical role in ESCC susceptibility.
- The PTPN23[Thr]-EGFR interaction is a key factor in ESCC development.
- Findings provide novel insights into the molecular mechanisms underlying ESCC pathogenesis.
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