P-316 - Mitochondrial ROS regulates hepatoma cell invasiveness via NFE2L1

Abstract

Many cancer cells require more glycolytic adenosine triphosphate production due to a mitochondrial respiratory defect. However, the roles of mitochondrial defects in cancer development and progression remain unclear. To address the role of transcriptomic regulation by mitochondrial defects in liver cancer cells, we performed gene expression profiling for three different cell models of mitochondrial defects: cells with chemical respiratory inhibition, cells with mitochondrial DNA depletion (Rho0), and liver cancer cells harboring mitochondrial defects. By comparing gene expression in the three models, we identified 10 common mitochondrial defect-related genes that may be responsible for retrograde signaling from cancer cell mitochondria to the intracellular transcriptome. The concomitant expression of the 10 common mitochondrial defect genes is significantly associated with poor prognostic outcomes in liver cancers, suggesting their functional and clinical relevance. Among the common mitochondrial defect genes, we found that NFE2L1 expression is regulated via mitochondrial reactive oxygen species (ROS) production levels and STAT3 activation. Currently, identification of key downstream effectors of STAT3/NFE2L1 axis to regulate hepatoma cell invasiveness.