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Oncotarget. 2017 Jul 27;8(34):55998-56020. doi: 10.18632/oncotarget.19639. eCollection 2017 Aug 22.

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

Author information

1
Unité Mixte de Recherche, Interactions Hôte-Greffon-Tumeur, Ingénierie Cellulaire et Génique, Université Bourgogne Franche-Comté, Besançon, France.
2
Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA.
3
Microvascular Endothelium and Neonatal Brain Lesions, Université de Normandie, UFR de Médecine et de Pharmacie, Rouen, France.
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Contributed equally

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.

KEYWORDS:

Autophagy; GABARAPL1; LC3; MCF-7; breast cancer

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