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Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas

Abstract : DCC (Deleted in Colorectal Carcinoma) has been demonstrated to constrain tumor progression by inducing apoptosis unless engaged by its ligand netrin-1. This has been shown in breast and colorectal cancers; however, this tumor suppressive function in other cancers is not established. Using a transgenic mouse model, we report here that inhibition of DCC-induced apoptosis is associated with lymphomagenesis. In human diffuse large B-cell lymphoma (DLBCL), an imbalance of the netrin-1/DCC ratio suggests a loss of DCC-induced apoptosis, either via a decrease in DCC expression in germinal center subtype or by up-regulation of netrin-1 in activated B-cell (ABC) one. Such imbalance is also observed in mantle cell lymphoma (MCL). Using a netrin-1 interfering antibody, we demonstrate both in vitro and in vivo that netrin-1 acts as a survival factor for ABC-DLBCL and MCL tumor cells. Together, these data suggest that interference with the netrin-1/DCC interaction could represent a promising therapeutic strategy in netrin-1-positive DLBCL and MCL
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Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Friday, February 5, 2016 - 2:17:13 PM
Last modification on : Friday, December 10, 2021 - 4:08:10 PM

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Laura Broutier, Marion Creveaux, Jonathan Vial, Antonin Tortereau, Jean-Guy Delcros, et al.. Targeting netrin-1/DCC interaction in diffuse large B-cell and mantle cell lymphomas. EMBO Molecular Medicine, Wiley Open Access, 2016, 8 (2), pp.96--104. ⟨10.15252/emmm.201505480⟩. ⟨hal-01269905⟩



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