The autophagy GABARAPL1 gene is epigenetically regulated in breast cancer models

自噬 GABARAPL1 基因在乳腺癌模型中受到表观遗传调控

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作者:Eric Hervouet, Aurore Claude-Taupin, Thierry Gauthier, Valérie Perez, Annick Fraichard, Pascale Adami, Gilles Despouy, Franck Monnien, Marie-Paule Algros, Michèle Jouvenot, Régis Delage-Mourroux, Michaël Boyer-Guittaut

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.

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.

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.

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