What this means
Researchers found a protein called PA200 helped lung tumors grow with age. Removing it reduced tumors in mice, so it may be a future target, but this does not show it treats people.
Plain-English summary written by an AI model from the abstract. The original is below.
- Who it was tested in
- Human lung cancer tissue and cells, plus mice with lung tumors
- Kind of research
- A study
The science
- Original title
- The p53-PA200 Feedback Loop Modulates Age-Dependent Tumorigenesis.
- Authors
- Jiang CY, Wang YL, Lv N et al.
- Journal
- International journal of molecular sciences
- Published
- Oct 16, 2026
- Study type
- Study · in humans
- PMID
- 42884025 ↗
Abstract
Tumor incidence increases markedly with advancing age, yet the molecular mechanisms linking aging-driven senescence to tumorigenesis remain incompletely understood. The proteasome activator PA200 preserves genomic stability by mediating the degradation of acetylated histones during aging. However, its function in age-associated tumor progression is poorly defined. Here, we demonstrate that PA200 promotes aging-associated tumorigenesis independent of its histone-degrading activity. Elevated PA200 correlates with poor prognosis and advancing age in human lung cancer. PA200-deficient tumor cells exhibit suppressed proliferation and migration, accompanied by aggravated oxidative-stress-triggered cellular senescence. Mechanistically, p53 directly binds and represses PSME4 transcription at its promoter. Reciprocally, PA200 facilitates proteasomal degradation of β-catenin, thereby sustaining p53 activity and forming a negative feedback loop. In the urethane-induced mouse lung tumor model, PA200 ablation markedly reduces tumor burden, especially in middle-aged mice. This effect is coupled with β-catenin accumulation, lowered p53 levels, and partial remodeling of the pro-inflammatory tumor microenvironment. Our findings uncover the p53-PA200-β-catenin feedback axis as a key driver of age-dependent lung tumorigenesis and highlight PA200 as a potential therapeutic target for elderly patients with lung cancer.
Jiang CY, Wang YL, Lv N et al. The p53-PA200 Feedback Loop Modulates Age-Dependent Tumorigenesis. International journal of molecular sciences. 2026. doi:10.3390/ijms27198783. PMID: 42884025. https://pubmed.ncbi.nlm.nih.gov/42884025/