XXXX -induced EMT promotes targeted migration of @entity0 cells through the lymphatic system by the activation of @entity13386 /CCL21-mediated chemotaxis.

@entity27619 @entity32 @entity13386 @entity0 @entity5 @entity641 @entity19 @entity1995
UNASSIGNED: @entity5 cells frequently disseminate through the lymphatic system during metastatic spread of @entity0 and many other types of @entity5 . Yet it is not clear how @entity5 cells make their way into the lymphatic system and how they choose between lymphatic and blood vessels for migration. Here we report that mammary @entity5 cells undergoing epithelial-mesenchymal transition (EMT) in response to transforming growth factor-b ( @entity641 ) become activated for targeted migration through the lymphatic system, similar to dendritic cells (DCs) during @entity32 . EMT cells preferentially migrated toward lymphatic vessels compared with blood vessels, both in vivo and in 3D cultures. A mechanism of this targeted migration was traced to the capacity of @entity641 to promote @entity13386 /CCL21-mediated crosstalk between @entity5 cells and lymphatic endothelial cells. On one hand, @entity641 promoted @entity13386 expression in EMT cells through @entity1995 MAP kinase-mediated activation of the @entity27619 transcription factor. Blockade of @entity13386 , or treatment with a @entity1995 MAP kinase inhibitor, reduced lymphatic dissemination of EMT cells in syngeneic @entity19 . On the other hand, @entity641 promoted CCL21 expression in lymphatic endothelial cells. CCL21 acted in a paracrine fashion to mediate chemotactic migration of EMT cells toward lymphatic endothelial cells. The results identify @entity641 -induced EMT as a mechanism, which activates @entity5 cells for targeted, DC-like migration through the lymphatic system. Furthermore, it suggests that @entity1995 MAP kinase inhibition may be a useful strategy to inhibit EMT and lymphogenic spread of @entity5 cells.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.133.
