The autophagy GABARAPL1 gene is epigenetically regulated in breast cancer models.

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Date publication

janvier 2015

Auteurs

Membres identifiés du Cancéropôle Est :
Dr ADAMI Pascale, Pr GUITTAUT Michaël, Pr DELAGE-MOURROUX Régis, Dr FRAICHARD Annick, Mr MONNIEN Franck, Dr HERVOUET Eric, Dr DESPOUY Gilles


Tous les auteurs :
Hervouet E, Claude-Taupin A, Gauthier T, Perez V, Fraichard A, Adami P, Despouy G, Monnien F, Algros MP, Jouvenot M, Delage-Mourroux R, Boyer-Guittaut M

Résumé

BACKGROUND: The GABARAP family members (GABARAP, GABARAPL1/GEC1 and GABARAPL2 /GATE-16) are involved in the intracellular transport of receptors and the autophagy pathway. We previously reported that GABARAPL1 expression was frequently downregulated in cancer cells while a high GABARAPL1 expression is a good prognosis marker for patients with lymph node-positive breast cancer. METHODS: In this study, we asked using qRT-PCR, western blotting and epigenetic quantification whether the expression of the GABARAP family was regulated in breast cancer by epigenetic modifications. RESULTS: Our data demonstrated that a specific decrease of GABARAPL1 expression in breast cancers was associated with both DNA methylation and histone deacetylation and that CREB-1 recruitment on GABARAPL1 promoter was required for GABARAPL1 expression. CONCLUSIONS: Our work strongly suggests that epigenetic inhibitors and CREB-1 modulators may be used in the future to regulate autophagy in breast cancer cells.

Référence

BMC Cancer. 2015 Oct 17;15:729