Carla Riera-Domingo, Eduarda Leite-Gomes, Iris Charatsidou, Peihua Zhao, Giovanna Carrá, Federica Cappellesso, Larissa Mourao, Maxim De Schepper, Dana Liu, Jens Serneels, Mohamad-Gabriel Alameh, Vladimir V Shuvaev, Tatjana Geukens, Edoardo Isnaldi, Hans Prenen, Drew Weissman, Vladimir R Muzykantov, Stefaan Soenen, Christine Desmedt, Colinda L G J Scheele, Anna Sablina, Mario Di Matteo, Rosa Martín-Pérez, Massimiliano Mazzone
Endothelial cells (ECs) grant access of disseminated cancer cells to distant organs. However, the molecular players regulating the activation of quiescent ECs at the premetastatic niche (PMN) remain elusive. Here, we find that ECs at the PMN coexpress tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its cognate death receptor 5 (DR5). Unexpectedly, endothelial TRAIL interacts intracellularly with DR5 to prevent its signaling and preserve a quiescent vascular phenotype. In absence of endothelial TRAIL, DR5 activation induces EC death and nuclear factor κB/p38-dependent EC stickiness, compromising vascular integrity and promoting myeloid cell infiltration, breast cancer cell adhesion, and metastasis...
March 22, 2023: Science Advances