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Publication : Semaphorin 3E suppresses tumor cell death triggered by the plexin D1 dependence receptor in metastatic breast cancers.

First Author  Luchino J Year  2013
Journal  Cancer Cell Volume  24
Issue  5 Pages  673-85
PubMed ID  24139859 Mgi Jnum  J:204681
Mgi Id  MGI:5538431 Doi  10.1016/j.ccr.2013.09.010
Citation  Luchino J, et al. (2013) Semaphorin 3E suppresses tumor cell death triggered by the plexin D1 dependence receptor in metastatic breast cancers. Cancer Cell 24(5):673-85
abstractText  The semaphorin guidance molecules and their receptors, the plexins, are often inappropriately expressed in cancers. However, the signaling processes mediated by plexins in tumor cells are still poorly understood. Here, we demonstrate that the Semaphorin 3E (Sema3E) regulates tumor cell survival by suppressing an apoptotic pathway triggered by the Plexin D1 dependence receptor. In mouse models of breast cancer, a ligand trap that sequesters Sema3E inhibited tumor growth and reduced metastasis through a selective tumor cytocidal effect. We further showed that Plexin D1 triggers apoptosis via interaction with the orphan nuclear receptor NR4A1. These results define a critical role of Sema3E/Plexin D1 interaction in tumor resistance to apoptosis and suggest a therapeutic approach based on activation of a dependence receptor pathway.
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