Circulating tumor cells with metastasis-initiating competence survive fluid shear stress during hematogenous dissemination through CXCR4-PI3K/AKT signaling.
Cancer Lett
; 590: 216870, 2024 May 28.
Article
em En
| MEDLINE
| ID: mdl-38614386
ABSTRACT
To seed lethal secondary lesions, circulating tumor cells (CTCs) must survive all rate-limiting factors during hematogenous dissemination, including fluid shear stress (FSS) that poses a grand challenge to their survival. We thus hypothesized that CTCs with the ability to survive FSS in vasculature might hold metastasis-initiating competence. This study reported that FSS of physiologic magnitude selected a small subpopulation of suspended tumor cells in vitro with the traits of metastasis-initiating cells, including stemness, migration/invasion potential, cellular plasticity, and biophysical properties. These shear-selected cells generated local and metastatic tumors at the primary and distal sites efficiently, implicating their metastasis competence. Mechanistically, FSS activated the mechanosensitive protein CXCR4 and the downstream PI3K/AKT signaling, which were essential in shear-mediated selection of metastasis-competent CTCs. In summary, these findings conclude that CTCs with metastasis-initiating competence survive FSS during hematogenous dissemination through CXCR4-PI3K/AKT signaling, which may provide new therapeutic targets for the early prevention of tumor metastasis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Células Neoplásicas Circulantes
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Lett
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Irlanda