Elevated GCN2 levels in cancer cells confer protection from mitotic stress and faster cell movement

PURPOSE: High expression of the stress-response kinase GCN2 has been linked to poor survival in several cancers including cervical cancer, but its underlying biological roles remain incompletely understood. This study aimed to identify genes whose expression correlates with GCN2 in locally advanced cervical cancer and to use these associations to elucidate cellular functions that could contribute to aggressive disease behavior. METHODS: Correlation analyses were performed between GCN2 expression and genome-wide mRNA profiles in a biobank of 291 patients with locally advanced cervical cancer. Gene ontology and pathway analyses were used to identify enriched biological processes, and functional assays were conducted to validate GCN2 involvement in selected pathways. RESULTS: GCN2 expression correlated not only with genes involved in cellular stress responses but also with those regulating mitosis and cell migration. Functional analyses confirmed that GCN2 activity promotes both proliferative and migratory capacities, revealing important cancer-relevant roles beyond its canonical function in translational control. CONCLUSION: Our findings demonstrate that elevated GCN2 levels support cellular functions that can contribute to tumor aggressiveness. These results suggest that GCN2 plays a direct role in malignant progression and may represent a potential biomarker or therapeutic target in locally advanced cervical cancer.