Show simple item record

dc.contributor.authorBrenet, Marianne
dc.contributor.authorMartínez, Samuel
dc.contributor.authorPérez-Núñez, Ramón
dc.contributor.authorPérez, Leonardo A.
dc.contributor.authorContreras, Pamela
dc.contributor.authorDíaz, Jorge E.
dc.contributor.authorÁvalos, Ana María
dc.contributor.authorSchneider, Pascal
dc.contributor.authorQuest, Andrew F.G.
dc.contributor.authorLeyton, Lisette
dc.date.accessioned2021-03-03T13:31:38Z
dc.date.available2021-03-03T13:31:38Z
dc.date.issued2021-01-12
dc.identifier10.3389/fcell.2020.592442
dc.identifier.issn2296634X
dc.identifier.urihttps://hdl.handle.net/20.500.12728/8642
dc.description.abstractAbstract View references (54) Cancer cell adhesion to the vascular endothelium is an important step in tumor metastasis. Thy-1 (CD90), a cell adhesion molecule expressed in activated endothelial cells, has been implicated in melanoma metastasis by binding to integrins present in cancer cells. However, the signaling pathway(s) triggered by this Thy-1-Integrin interaction in cancer cells remains to be defined. Our previously reported data indicate that Ca2+-dependent hemichannel opening, as well as the P2X7 receptor, are key players in Thy-1-αVβ3 Integrin-induced migration of reactive astrocytes. Thus, we investigated whether this signaling pathway is activated in MDA-MB-231 breast cancer cells and in B16F10 melanoma cells when stimulated with Thy-1. In both cancer cell types, Thy-1 induced a rapid increase in intracellular Ca2+, ATP release, as well as cell migration and invasion. Connexin and Pannexin inhibitors decreased cell migration, implicating a requirement for hemichannel opening in Thy-1-induced cell migration. In addition, cell migration and invasion were precluded when the P2X7 receptor was pharmacologically blocked. Moreover, the ability of breast cancer and melanoma cells to transmigrate through an activated endothelial monolayer was significantly decreased when the β3 Integrin was silenced in these cancer cells. Importantly, melanoma cells with silenced β3 Integrin were unable to metastasize to the lung in a preclinical mouse model. Thus, our results suggest that the Ca2+/hemichannel/ATP/P2X7 receptor-signaling axis triggered by the Thy-1-αVβ3 Integrin interaction is important for cancer cell migration, invasion and transvasation. These findings open up the possibility of therapeutically targeting the Thy-1-Integrin signaling pathway to prevent metastasis.es_ES
dc.language.isoenes_ES
dc.publisherFrontiers Media S.A.es_ES
dc.subjectbreast canceres_ES
dc.subjectinflammationes_ES
dc.subjectintegrines_ES
dc.subjectmelanomaes_ES
dc.subjectmetastasises_ES
dc.subjectP2X7Res_ES
dc.subjectThy-1 (CD90)es_ES
dc.subjecttrans-endothelial migrationes_ES
dc.titleThy-1 (CD90)-Induced Metastatic Cancer Cell Migration and Invasion Are β3 Integrin-Dependent and Involve a Ca2+/P2X7 Receptor Signaling Axises_ES
dc.typeArticlees_ES


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record