Cancer cells live in a hostile microenvironment where they are exposed to several different types of stress, such as poor nutrient and oxygen supply. The standing view is that cancer cells are therefore more dependent on stress-response pathways than normal cells are. GCN2 is known as a major player in several stress-response pathways, and therefore it is considered to be a potential target for therapy.
We have analyzed GCN2 expression levels in a biobank of tumour samples from more than 500 cervical cancer patients (ongoing collaboration with Heidi Lyng at the Department of Radiation Biology). GCN2 mRNA level is elevated in many samples and high level of expression correlates with poor prognosis. Interestingly, our pathway analyses of genes correlating with GCN2 expression in the biobank identified not only stress responses, but also genes involved in other pathways as significantly correlating with GCN2 levels, suggesting novel functions. One of the novel functions indicated by this analysis is inmitosis. This has been a major focus of our work and I will present our results. In light of these findings we suggest that, in addition to stress responses, GCN2 has important functions other than stress responses relevant for carcinogenesis. This has implications for any therapeutic strategy targeting GCN2, since it will attack cancer cells on several fronts.