Direct evidence of cellular transformation by prion-like p53 amyloid infection.
J Cell Sci
; 134(11)2021 06 01.
Article
en En
| MEDLINE
| ID: mdl-34085695
ABSTRACT
Tumor suppressor p53 mutations are associated with more than 50% of cancers. Aggregation and amyloid formation of p53 is also implicated in cancer pathogenesis, but direct evidence for aggregated p53 amyloids acting as an oncogene is lacking. Here, we conclusively demonstrate that wild-type p53 amyloid formation imparts oncogenic properties to non-cancerous cells. p53 amyloid aggregates were transferred through cell generations, contributing to enhanced survival, apoptotic resistance with increased proliferation and migration. The tumorigenic potential of p53 amyloid-transformed cells was further confirmed in mouse xenografts, wherein the tumors showed p53 amyloids. p53 disaggregation rescued the cellular transformation and inhibited tumor development in mice. We propose that wild-type p53 amyloid formation contributes to tumorigenesis and can be a potential target for therapeutic intervention. This article has an associated First Person interview with the first author of the paper.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Priones
/
Neoplasias
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article