Oncotarget

Research Papers:

YM155 potently triggers cell death in breast cancer cells through an autophagy-NF-kB network

Eloïse Véquaud _, Céline Séveno, Delphine Loussouarn, Lucie Engelhart, Mario Campone, Philippe Juin and Sophie Barillé-Nion

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Oncotarget. 2015; 6:13476-13486. https://doi.org/10.18632/oncotarget.3638

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Abstract

Eloïse Véquaud1, Céline Séveno1, Delphine Loussouarn1,2, Lucie Engelhart1, Mario Campone1,3, Philippe Juin1,3, Sophie Barillé-Nion1

1CRCNA, UMR INSERM U892, CNRS 6299, Université de Nantes, Team 8 « Cell Survival and Tumor Escape in Breast Cancers », Institut de Recherche en Santé de l’Université de Nantes, Nantes, France

2Service d’Anatomie Pathologique, HGRL, CHU, Nantes University, Nantes, France

3Institut de Cancérologie de Nantes, Centre de lutte contre le Cancer René Gauducheau, Boulevard Jacques Monod, Nantes, France

Correspondence to:

Sophie Barillé-Nion, e-mail: sophie.barille@inserm.fr

Keywords: breast cancer, therapy, ex vivo assay

Received: December 09, 2014     Accepted: April 25, 2015     Published: May 06, 2015

ABSTRACT

Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first “Survivin suppressant” but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. We herein show that YM155 exerts single agent toxicity on primary breast cancer cells grown in an ex vivo assay preserving tumor microenvironment. In vitro assays indicate that YM155 more efficiently triggers cell death in breast cancer cells (including these with stem-cell like properties) than in non tumorigenic mammary cells. YM155-induced cell death is critically dependent on autophagy and NF-kB but independent of p53 and it coïncides with DNA damage and a DNA damage response in p53-proficient cells. Our results point out a crosstalk between NF-kB and autophagy controlling YM155-induced death in breast cancer cells and argue for the potential use of YM155 as a genotoxic agent in breast cancer therapy.


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