Tumor-induced endothelial RhoA activation mediates tumor cell transendothelial migration and metastasis
Sajib, M. S.; Zahra, F. T.; Lamprou, M.; Akwii, R. G.; Park, J. H.; Osorio, M.; Tullar, P.; Doci, C. L.; Zhang, C.; Huveneers, S.; van Buul, J. D.; Wang, M.-H.; Markiewski, M. M.; Srivastava, S. K.; Zheng, Y.; Gutkind, J. S.; Hu, J.; Bickel, U.; Maeda, D. Y.; Zebala, J. A.; Lionakis, M. S.; Trasti, S.; Mikelis, C. M.
Show abstract
Abstract/SummaryThe 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 {beta}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.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- MAGI1 inhibits the AMOTL2/p38 stress pathway and prevents luminal breast tumorigenesis 96%
- Oncogenic signaling inhibits c-FLIP expression and promotes cancer cell survival during ECM-detachment 95%
- Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A 94%
Similar papers in this journal
- Decorin, a novel negative modulator of E-cadherin in inflammatory breast cancer 96%
- Glycocalyx-Mediated Vascular Dissemination of Circulating Tumor Cells 95%
- Neutrophil Extracellular Trap gene expression signatures identify prognostic and targetable signaling axes for inhibiting metastasis of pancreatic tumours 95%
Similar papers in this journal
- Versatile roles of Annexin A4 in ccRCC: impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment 95%
- Mesenchymal-epithelial transition reduces proliferation but increases immune evasion in tumor spheroids 95%
- Tumor expressed CD95 causes suppression of anti-tumor activity of NK cells in a model of triple negative breast cancer 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.