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Article Dans Une Revue EMBO Molecular Medicine Année : 2016

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

Céline Pangault
Nicolas Gadot
  • Fonction : Auteur
Olivier Donzé
  • Fonction : Auteur
Gilles Salles

Résumé

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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Dates et versions

hal-01269905 , version 1 (28-02-2024)

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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, 2016, 8 (2), pp.96--104. ⟨10.15252/emmm.201505480⟩. ⟨hal-01269905⟩
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