GABARAPL1 tumor suppressive function is independent of its conjugation to autophagosomes in MCF-7 breast cancer cells.
Fiche publication
Date publication
août 2017
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BORG Christophe, Pr GUITTAUT Michaël, Pr DELAGE-MOURROUX Régis, Dr FRAICHARD Annick, Dr HERVOUET Eric, Dr DESPOUY Gilles
Tous les auteurs :
Poillet-Perez L, Jacquet M, Hervouet E, Gauthier T, Fraichard A, Borg C, Pallandre JR, Gonzalez BJ, Ramdani Y, Boyer-Guittaut M, Delage-Mourroux R, Despouy G
Lien Pubmed
Résumé
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.
Mots clés
Autophagy, GABARAPL1, LC3, MCF-7, breast cancer
Référence
Oncotarget. 2017 Aug;8(34):55998-56020