Coordinated by Professor Michaël GUITTAUT, the “AETIC” group focuses on deciphering the role of autophagy effectors from the ATG8 family as well as their post-transcriptional regulation (NMD) in various cancers, while also investigating epigenetic modifications occurring during tumor development.
The group is oriented around three projects:
Project 1: The expression and role of ATG8 proteins in cancer remain largely unknown and controversial. However, the group recently demonstrated that the expression of GABARAPL1 (a member of the ATG8 family) correlates with markers of EMT (Epithelial-Mesenchymal Transition) in lung adenocarcinomas, and that the product of this gene may be involved in a negative feedback loop of EMT. Indeed, EMT induction leads to increased levels of GABARAPL1 via activation of the SMAD signaling pathway. GABARAPL1 then induces the degradation of SMAD factors within autophagosomes, resulting in inhibition of the transcription factor SNAIL—an established SMAD target—and consequently of EMT. A second aspect of this project aims to determine whether GABARAPL1 transcript levels are regulated during EMT by the mRNA degradation process known as NMD (Nonsense-mediated mRNA decay).
Project 2: Autophagy has been described as playing an important role in the immune response, particularly in the presentation of antigenic peptides by MHC. In the laboratory, the group has shown that GABARAP and GABARAPL1 proteins can be used to target specific antigens to autophagosomes, enhance their presentation by MHC class II, and thereby specifically activate CD4+ T lymphocyte responses.
Project 3: Epigenetics is a key mechanism involved in gene regulation under both normal and pathological conditions. This is why, in 2016, the EPIGENExp platform was created, dedicated to the study of cellular epigenetic processes. The research axes focus on:
- Characterizing the role of two key epigenetic enzymes, EZH2 and KDM6B, during EMT
- Studying the epigenetic regulation of autophagy-related genes
- Epigenetic reprogramming of tumor-infiltrating T lymphocytes to improve anti-tumor immune responses
- Identifying new epigenetic biomarkers of cancer through the study of circulating tumor DNA
