The NMD Pathway Regulates mRNA during the EMT.

EMT is a reversible cellular process that is linked to gene expression reprogramming, which allows for epithelial cells to undergo a phenotypic switch to acquire mesenchymal properties. EMT is associated with cancer progression and cancer therapeutic resistance and it is known that, during the EMT, many stress response pathways, such as autophagy and NMD, are dysregulated. Therefore, our goal was to study the regulation of ATG8 family members (, ) by the NMD and to identify molecular links between these two cellular processes that are involved in tumor development and metastasis formation. IHC experiments, which were conducted in a cohort of patients presenting lung adenocarcinomas, showed high and low levels in EMT+ tumors. We observed increased levels of correlated with decreased levels of NMD factors in A549 cells in vitro. We then confirmed that mRNA was indeed targeted by the NMD in a -dependent manner and we identified four overlapping binding sites for and that are potentially involved in the recognition of this transcript by the NMD pathway. Our study suggests that -dependent NMD might be an important mechanism that is involved in the induction of autophagy and could represent a promising target in the development of new anti-cancer therapies.