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
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Neoplastic Cells, Circulating
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cancer Lett
Year:
2024
Document type:
Article
Affiliation country:
China