T Renno’ team / C Chaveroux’s Group

Nutritional stress response

Malignant cells are characterized by an altered metabolism compared to normal cells, aiming at supporting their dysregulated proliferation. Particularly, increased nutrients uptake and metabolic flux, subsequently to activation of the oncogenic signaling such as the RAS pathway, support the generation of biomass and energetic processes. However, throughout cancer progression, the elevated demand for nutrients and the poorly organized vasculature of tumors can lead to nutritional exhaustion in the microenvironment. In addition, tumors cells are sometimes subjected to therapeutic intervention based on nutritional starvation. How tumor cells respond to this stress is challenging. Cellular outcome following these stresses will rely on the activity of molecular mechanisms and downstream signaling pathway supporting cell adaptation or death. In this context, our group relies on expertise in i) in vivo and in vitro modeling of the altered nutritional microenvironment occurring in tumors. In particular, we are focusing our interest on the relevance of the stress pathway controlled by the nutrient sensor: GCN2, and its targeting for anticancer treatments.