Novel cancer-related roles of GCN2
2020
Sharma Humagain, Prabin
GCN2, an amino-acid deprivation sensor is one of the kinases activated during the integrated stress response. Its role in normal as well as in cancer cells during stress induced by starvation has garnered a lot of attention. Most of the literature describes GCN2’s role based on its action on the eIF2-ATF4 pathway. However, recent findings suggest that this may not be the only way that GCN2 acts and may not be the only reason why it is important in the context of cancer. Therefore, our group began a study of transcriptomic data from cervical cancer patients to analyze the correlation of various genes with GCN2 and found different functional groups associated with the genes that showed correlation with GCN2. So, in this study, we performed correlation analyses for selected groups of genes using different cell lines. We found that there is a correlation between GCN2 and genes associated with cell motility, mitosis, oxidative phosphorylation, and immune response. Based on these results, phenotypic analyses were done. We were also able to show through phenotypic analysis that GCN2 has a role in directional migration while our preliminary result also suggests an increase in mitochondrial respiration in the case of GCN2 depletion. This study has been successful in verifying the correlation of GCN2 with some genes that are important in cancer survival and was also able to prove the role of GCN2 in pathways other than the ISR relevant to cancer. Further investigation of the findings of this study could prove valuable in understanding the role of GCN2 and using it as a target in therapy against cancer.
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