Survivin-3B potentiates immune escape in cancer but also inhibits the toxicity of cancer chemotherapy.

Fiche publication

Date publication

septembre 2013


Membres identifiés du Cancéropôle Est :
Dr ARNOULD Laurent, Dr BOIDOT Romain, Dr LIZARD Sarab, Dr MIRJOLET Céline, Dr COLLIN Bertrand, Dr VEGRAN Frédérique, Dr CHARON-BARRA Céline

Tous les auteurs :
Vegran F, Mary R, Gibeaud A, Mirjolet C, Collin B, Oudot A, Charon-Barra C, Arnould L, Lizard-Nacol S, Boidot R


Dysregulation in patterns of alternative RNA splicing in cancer cells is emerging as a significant factor in cancer pathophysiology. In this study, we investigated the little known alternative splice isoform survivin-3B (S-3B) that is overexpressed in a tumor-specific manner. Ectopic overexpression of S-3B drove tumorigenesis by facilitating immune escape in a manner associated with resistance to immune cell toxicity. This resistance was mediated by interaction of S-3B with procaspase-8, inhibiting death-inducing signaling complex formation in response to Fas/Fas ligand interaction. We found that S-3B overexpression also mediated resistance to cancer chemotherapy, in this case through interactions with procaspase-6. S-3B binding to procaspase-6 inhibited its activation despite mitochondrial depolarization and caspase-3 activation. When combined with chemotherapy, S-3B targeting in vivo elicited a nearly eradication of tumors. Mechanistic investigations identified a previously unrecognized 7-amino acid region as responsible for the procancerous properties of survivin proteins. Taken together, our results defined S-3B as an important functional actor in tumor formation and treatment resistance.


Cancer Res. 2013 Sep 1;73(17):5391-401