The autophagy GABARAPL1 gene is epigenetically regulated in breast cancer models

BMC Cancer. 2015 Oct 17:15:729. doi: 10.1186/s12885-015-1761-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Autophagy / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cyclic AMP Response Element-Binding Protein / genetics*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA Methylation / genetics*
  • Epigenomics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Promoter Regions, Genetic

Substances

  • Adaptor Proteins, Signal Transducing
  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • GABARAPL1 protein, human
  • Histones
  • Microtubule-Associated Proteins