Oncotarget

Research Papers: Autophagy and Cell Death:

GABARAPL1 tumor suppressive function is independent of its conjugation to autophagosomes in MCF-7 breast cancer cells

Laura Poillet-Perez, Marine Jacquet, Eric Hervouet, Thierry Gauthier, Annick Fraichard, Christophe Borg, Jean-René Pallandre, Bruno J. Gonzalez, Yasmina Ramdani, Michaël Boyer-Guittaut, Régis Delage-Mourroux and Gilles Despouy _

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Oncotarget. 2017; 8:55998-56020. https://doi.org/10.18632/oncotarget.19639

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Abstract

Laura Poillet-Perez1,3,* Marine Jacquet1,* Eric Hervouet1, Thierry Gauthier1, Annick Fraichard1, Christophe Borg1, Jean-René Pallandre1, Bruno J. Gonzalez2, Yasmina Ramdani2, Michaël Boyer-Guittaut1, Régis Delage-Mourroux1 and Gilles Despouy1

1 Unité Mixte de Recherche, Interactions Hôte-Greffon-Tumeur, Ingénierie Cellulaire et Génique, Université Bourgogne Franche-Comté, Besançon, France

2 Microvascular Endothelium and Neonatal Brain Lesions, Université de Normandie, UFR de Médecine et de Pharmacie, Rouen, France

3 Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA

* These authors have contributed equally to this work

Correspondence to:

Gilles Despouy, email:

Keywords: breast cancer, GABARAPL1, LC3, MCF-7, Autophagy

Received: August 02, 2016 Accepted: July 18, 2017 Published: July 27, 2017

Abstract

The GABARAPL1 protein belongs to the ATG8 family whose members are involved in autophagy. Our laboratory previously demonstrated that GABARAPL1 associates with autophagic vesicles, regulates autophagic flux and acts as a tumor suppressor protein in breast cancer. In this study, we aimed to determine whether GABARAPL1 conjugation to autophagosomes is necessary for its tumor suppressive functions using the MCF-7 breast cancer cell line overexpressing GABARAPL1 or a G116A mutant, which is unable to be lipidated and associated to autophagosomes. We show that the G116A mutation impaired GABARAPL1 function in autophagosome/lysosome fusion and inhibited lysosome activity but did not alter MTOR and ULK1 activities or tumor growth in vivo. Our results demonstrate for the first time that GABARAPL1 plays different regulatory functions during early and late stages of autophagy, independently or not of its conjugation to autophagosomes, but its tumor suppressive function appeared to be independent of its conjugation to autophagic vesicles.


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