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The autophagy GABARAPL1 gene is epigenetically regulated in breast cancer models
Eric Hervouet1, Aurore Claude-Taupin2, Thierry Gauthier3
1Université de Franche-Comté, Laboratoire de Biochimie, EA3922 « Estrogènes, Expression Génique et Pathologies du Système Nerveux Central », SFR IBCT FED4234, UFR Sciences et Techniques, 16 route de Gray, 25030, Besançon Cedex, France. eric.hervouet@univ-fcomte.fr.
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.
Insights
Breast cancer cells frequently downregulate GABARAPL1 expression due to epigenetic changes like DNA methylation and histone deacetylation. Modulating these epigenetic factors may offer new therapeutic strategies for breast cancer.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- The GABARAP family (GABARAP, GABARAPL1, GABARAPL2) plays a role in intracellular transport and autophagy.
- GABARAPL1 expression is often reduced in cancer cells and serves as a positive prognostic marker in lymph node-positive breast cancer.
Purpose of the Study:
- To investigate whether epigenetic modifications regulate GABARAP family expression in breast cancer.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR)
- Western blotting
- Epigenetic quantification techniques
Main Results:
- A decrease in GABARAPL1 expression in breast cancer correlates with DNA methylation and histone deacetylation.
- CREB-1 recruitment to the GABARAPL1 promoter is essential for its expression.
Conclusions:
- Epigenetic alterations significantly impact GABARAPL1 expression in breast cancer.
- Epigenetic inhibitors and CREB-1 modulators show potential for regulating autophagy in breast cancer treatment.
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