Involvement of mitochondrial defects in liver cancer progression

5^th World Congress on Cancer Therapy

September 28-30, 2015 Atlanta, USA

Young-Kyoung Lee and Gyesoon Yoon

Ajou University School of Medicine, Korea

Posters-Accepted Abstracts: J Cancer Sci Ther

Abstract :

Many cancer cells require more glycolytic ATP 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 by mitochondrial defects and accompanied glycolytic activation in liver cancer cells, we employed diverse cell models of mitochondrial defects: cells with chemical respiratory inhibition, cells with mitochondrial DNA depletion (ρ0), liver cancer cells harboring mitochondrial defects, and oncogenic transfomation with K-ras-mediated mitochondrial dysfunction. We demonstrated that oncogenic K-ras triggered autophagy-mediated mitochondrial degradation and glycolytic activation during the transformation process. In addition, we proved that mitochondrial respiratory defects enhanced Cln-1-mediated hepatoma cell invasiveness via mitochondrial ROS-mediated HSF1 activation. Finally, by comparing gene expression in the three cell models with mitochondrial defect, we identified 10 common mitochondrial defect (CMD)��?related genes that may be responsible for retrograde signaling from cancer cell mitochondria to the intracellular transcriptome. The concomitant expression of the 10 CMD genes is significantly associated with poor prognostic outcomes in liver cancers, suggesting their functional and clinical relevance. We suggest that mitochondrial respiratory defects and subsequent retrograde signaling play pivotal roles in liver cancer progression.

Biography :

Email: ypeace@ajou.ac.kr