PTPN23[Thr] variant reduces susceptibility and tumorigenesis in esophageal squamous cell carcinoma through dephosphorylation of EGFR.
Cancer Lett
; 592: 216936, 2024 Jun 28.
Article
en En
| MEDLINE
| ID: mdl-38704135
ABSTRACT
Post-translational modifications (PTMs) have emerged as pivotal regulators of the development of cancers, including esophageal squamous cell carcinoma (ESCC). Here, we conducted a comprehensive analysis of PTM-related genetic variants associated with ESCC risk using large-scale genome-wide and exome-wide association datasets. We observed significant enrichment of PTM-related variants in the ESCC risk loci and identified five variants that were significantly associated with ESCC risk. Among them, rs6780013 in PTPN23 exhibited the highest level of significance in ESCC susceptibility in 9,728 ESCC cases and 10,977 controls (odds ratio [OR] = 0.85, 95 % confidence interval [CI] = 0.81- 0.89, P = 9.77 × 10-14). Further functional investigations revealed that PTPN23[Thr] variant binds to EGFR and modulates its phosphorylation at Thr699. PTPN23[Thr] variant substantially inhibited ESCC cell proliferation both in vitro and in vivo. Our findings underscore the critical role of PTPN23[Thr]-EGFR interaction in ESCC development, providing more insights into the pathogenesis of this cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Esofágicas
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Predisposición Genética a la Enfermedad
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Proliferación Celular
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Receptores ErbB
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Carcinoma de Células Escamosas de Esófago
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Lett
Año:
2024
Tipo del documento:
Article
País de afiliación:
China