Matches in SemOpenAlex for { <https://semopenalex.org/work/W3174473362> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W3174473362 abstract "Metastasis is the cause of more than 90% of cancer-related deaths. An important step in metastatic process is the migration of the disseminating cancer cells through the endothelial monolayer during entrance or exit from the vasculature. Activation of endothelial RhoA-ROCK pathway has been implicated in the regulation of vascular permeability in various pathophysiological conditions. In the present study, we have investigated the role of this pathway in trans-endothelial migration and metastasis of breast cancer cells. RhoA activation was identified by RhoA pull-down experiments of murine and human breast cancer cell supernatant on primary endothelial cells. Cancer cell trans-endothelial migration efficiency was explored through an in vitro transwell-based two-cell co-culture model. RhoA signaling pathway was blocked by both pharmacological inhibition and knockdown experiments. In vivo metastatic potential was identified by experimental metastasis models of murine and human breast cancer cell lines using endothelial-specific RhoA-deficient mice or clinically relevant ROCK inhibitors. We identified that the diverse metastatic potential of a panel of human breast cancer cell lines correlated with the RhoA activation efficiency of their supernatant on primary endothelial cells. Secretome analysis revealed that IL-8 (over)expression was relevant to breast cancer cell aggressiveness and its functionality was tested with gain-and loss-of-function experiments. In vivo, experimental metastasis experiments with the syngeneic breast cancer cell line E0771 showed that endothelial RhoA deficiency decreased the metastatic potential. Similar inhibition was obtained with treatment with the clinically-relevant ROCK inhibitor, Fasudil, in experimental metastasis experiments of murine and human cell lines using immune-competent and immune-deficient mice respectively. Collectively, our in vitro and in vivo findings demonstrate that the endothelial RhoA-ROCK pathway affects breast cancer trans-endothelial migration and metastasis and propose endothelial RhoA inhibition as a novel therapy for breast cancer metastases. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal." @default.
- W3174473362 created "2021-07-05" @default.
- W3174473362 creator A5011788316 @default.
- W3174473362 creator A5022942037 @default.
- W3174473362 creator A5037387913 @default.
- W3174473362 creator A5056153725 @default.
- W3174473362 creator A5063507385 @default.
- W3174473362 creator A5074011935 @default.
- W3174473362 creator A5082705765 @default.
- W3174473362 date "2019-04-01" @default.
- W3174473362 modified "2023-10-14" @default.
- W3174473362 title "Endothelial RhoA Regulates Breast Cancer Metastasis" @default.
- W3174473362 doi "https://doi.org/10.1096/fasebj.2019.33.1_supplement.647.40" @default.
- W3174473362 hasPublicationYear "2019" @default.
- W3174473362 type Work @default.
- W3174473362 sameAs 3174473362 @default.
- W3174473362 citedByCount "0" @default.
- W3174473362 crossrefType "journal-article" @default.
- W3174473362 hasAuthorship W3174473362A5011788316 @default.
- W3174473362 hasAuthorship W3174473362A5022942037 @default.
- W3174473362 hasAuthorship W3174473362A5037387913 @default.
- W3174473362 hasAuthorship W3174473362A5056153725 @default.
- W3174473362 hasAuthorship W3174473362A5063507385 @default.
- W3174473362 hasAuthorship W3174473362A5074011935 @default.
- W3174473362 hasAuthorship W3174473362A5082705765 @default.
- W3174473362 hasConcept C121608353 @default.
- W3174473362 hasConcept C123012128 @default.
- W3174473362 hasConcept C126322002 @default.
- W3174473362 hasConcept C137738243 @default.
- W3174473362 hasConcept C1491633281 @default.
- W3174473362 hasConcept C150903083 @default.
- W3174473362 hasConcept C185592680 @default.
- W3174473362 hasConcept C202751555 @default.
- W3174473362 hasConcept C207001950 @default.
- W3174473362 hasConcept C2775930923 @default.
- W3174473362 hasConcept C2777093181 @default.
- W3174473362 hasConcept C2779013556 @default.
- W3174473362 hasConcept C502942594 @default.
- W3174473362 hasConcept C530470458 @default.
- W3174473362 hasConcept C54355233 @default.
- W3174473362 hasConcept C55493867 @default.
- W3174473362 hasConcept C62478195 @default.
- W3174473362 hasConcept C71924100 @default.
- W3174473362 hasConcept C81885089 @default.
- W3174473362 hasConcept C86803240 @default.
- W3174473362 hasConcept C95444343 @default.
- W3174473362 hasConcept C96232424 @default.
- W3174473362 hasConceptScore W3174473362C121608353 @default.
- W3174473362 hasConceptScore W3174473362C123012128 @default.
- W3174473362 hasConceptScore W3174473362C126322002 @default.
- W3174473362 hasConceptScore W3174473362C137738243 @default.
- W3174473362 hasConceptScore W3174473362C1491633281 @default.
- W3174473362 hasConceptScore W3174473362C150903083 @default.
- W3174473362 hasConceptScore W3174473362C185592680 @default.
- W3174473362 hasConceptScore W3174473362C202751555 @default.
- W3174473362 hasConceptScore W3174473362C207001950 @default.
- W3174473362 hasConceptScore W3174473362C2775930923 @default.
- W3174473362 hasConceptScore W3174473362C2777093181 @default.
- W3174473362 hasConceptScore W3174473362C2779013556 @default.
- W3174473362 hasConceptScore W3174473362C502942594 @default.
- W3174473362 hasConceptScore W3174473362C530470458 @default.
- W3174473362 hasConceptScore W3174473362C54355233 @default.
- W3174473362 hasConceptScore W3174473362C55493867 @default.
- W3174473362 hasConceptScore W3174473362C62478195 @default.
- W3174473362 hasConceptScore W3174473362C71924100 @default.
- W3174473362 hasConceptScore W3174473362C81885089 @default.
- W3174473362 hasConceptScore W3174473362C86803240 @default.
- W3174473362 hasConceptScore W3174473362C95444343 @default.
- W3174473362 hasConceptScore W3174473362C96232424 @default.
- W3174473362 hasIssue "S1" @default.
- W3174473362 hasLocation W31744733621 @default.
- W3174473362 hasOpenAccess W3174473362 @default.
- W3174473362 hasPrimaryLocation W31744733621 @default.
- W3174473362 hasRelatedWork W2259137911 @default.
- W3174473362 hasRelatedWork W2391617054 @default.
- W3174473362 hasRelatedWork W2790145453 @default.
- W3174473362 hasRelatedWork W2904294837 @default.
- W3174473362 hasRelatedWork W3033874287 @default.
- W3174473362 hasRelatedWork W3119915123 @default.
- W3174473362 hasRelatedWork W3174473362 @default.
- W3174473362 hasRelatedWork W4283771460 @default.
- W3174473362 hasRelatedWork W4304116770 @default.
- W3174473362 hasRelatedWork W4306385347 @default.
- W3174473362 hasVolume "33" @default.
- W3174473362 isParatext "false" @default.
- W3174473362 isRetracted "false" @default.
- W3174473362 magId "3174473362" @default.
- W3174473362 workType "article" @default.