About the Project

Cellular plasticity and survival requires adaptation to challenging environmental conditions. This is achieved through activation of different stress-response pathways, such as the Integrated Stress Response (ISR), the response to oxidative/electrophilic stress and the response to low oxygen (hypoxia). These pathways leading to activation of transcription factors ATF4, NRF2 and HIF, respectively, are also exploited by cancer cells in order to survive in the harsh tumor microenvironment. Distinct stress-response pathways do not function in isolation but are rather parts of operating cellular networks, as cells encounter a wide variety of stress conditions. Determining how different stress pathways are integrated within a cell can allow their simultaneous targeting in order to eliminate tumor cells without inducing drug resistance. Although the aforementioned critical pathways influence each other, their crosstalk and their synergistic effect at genome-wide level is poorly understood. The principal aim of INTEROXYSTRESS is thorough analysis and understanding of the mechanistic and functional connections between the cellular response to hypoxia, the ISR and NRF2 activation.