| Autor: |
Sajib MS, Zahra FT, Lamprou M, Akwii RG, Park JH, Osorio M, Tullar P, Doci CL, Zhang C, Huveneers S, Van Buul JD, Wang MH, Markiewski MM, Srivastava SK, Zheng Y, Gutkind JS, Hu J, Bickel U, Maeda DY, Zebala JA, Lionakis MS, Trasti S, Mikelis CM |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 24. Date of Electronic Publication: 2024 Sep 24. |
| DOI: |
10.1101/2024.09.22.614304 |
| Abstrakt: |
The endothelial barrier plays an active role in transendothelial tumor cell migration during metastasis, however, the endothelial regulatory elements of this step remain obscure. Here we show that endothelial RhoA activation is a determining factor during this process. Breast tumor cell-induced endothelial RhoA activation is the combined outcome of paracrine IL-8-dependent and cell-to-cell contact β 1 integrin-mediated mechanisms, with elements of this pathway correlating with clinical data. Endothelial-specific RhoA blockade or in vivo deficiency inhibited the transendothelial migration and metastatic potential of human breast tumor and three murine syngeneic tumor cell lines, similar to the pharmacological blockade of the downstream RhoA pathway. These findings highlight endothelial RhoA as a potent, universal target in the tumor microenvironment for anti-metastatic treatment of solid tumors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
