TP53 mutation at codon 179 metabolically reprograms cancer cells to promote invasion
TP53 missense mutations at codon 179 act as oncogenic drivers, reprogramming cellular metabolism and enhancing invasive potential in multiple cancer types
Mutations in the tumour suppressor TP53 are frequently observed in human cancers, yet their functional impact varies. Through pan‑cancer database analysis we identified H179 TP53 mutations as associated with poor disease‑free survival across multiple tumour types, especially non‑small cell lung cancer. Functional assays in lung, ovarian and prostate cancer cell lines over‑expressing p53H179R/Y mutants showed loss of canonical p53 activity coupled with metabolic reprogramming—elevated neutral lipid content via de novo fatty‑acid synthesis and uptake, increased lipid droplets, APOE expression, and enhanced invasiveness. These findings demonstrate that H179 TP53 mutations serve as oncogenic drivers and highlight APOE and lipid‑metabolism pathways as potential therapeutic targets.
H179 TP53 mutations are linked to worse prognosis and confer resistance to typical tumour‑suppressive responses, indicating the need for mutation‑specific therapeutic strategies that target altered lipid metabolism.
Bizonyítékszint: Állatkísérletes. Állatmodellben vizsgálták.
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