Gain-of-function p53 protein transferred via small extracellular vesicles promotes conversion of fibroblasts to a cancer-associated phenotype.
Cell Rep
; 34(6): 108726, 2021 02 09.
Article
em En
| MEDLINE
| ID: mdl-33567287
ABSTRACT
Tumor and stromal interactions consist of reciprocal signaling through cytokines, growth factors, direct cell-cell interactions, and extracellular vesicles (EVs). Small EVs (≤200 nm) have been considered critical messengers of cellular communication during tumor development. Here, we demonstrate that gain-of-function (GOF) p53 protein can be packaged into small EVs and transferred to fibroblasts. GOF p53 protein is selectively bound by heat shock protein 90 (HSP90), a chaperone protein, and packaged into small EVs. Inhibition of HSP90 activity blocks packaging of GOF, but not wild-type, p53 in small EVs. GOF p53-containing small EVs result in their conversion to cancer-associated fibroblasts. In vivo studies reveal that GOF p53-containing small EVs can enhance tumor growth and promote fibroblast transformation into a cancer-associated phenotype. These findings provide a better understanding of the complex interactions between cancer and stromal cells and may have therapeutic implications.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína Supressora de Tumor p53
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Vesículas Extracelulares
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Fibroblastos Associados a Câncer
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Mutação com Ganho de Função
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos