KrasG12D-LOH promotes malignant biological behavior and energy metabolism of pancreatic ductal adenocarcinoma cells through the mTOR signaling pathway

Oncogenic Kras with loss of heterozygosity (LOH) is frequently detected in various tumours. However, the exact function and mechanism by which Kras'D-LOH operates remain unclear. Therefore, the current study investigated the effect of Kras(G12D)-LOH on the malignant phenotype of pancreatic ductal adenocarcinoma (PDAC) cells. Our investigation revealed that Kras(G12D)-1,0I1 is associated with increased proliferation, invasion and reduced apoptosis in PDAC cells. The results also exhibited enhanced glycolytic phenotype of Kras(G12D)-LOH PDAC cells. Hyperactive mTOR plays a significant role in the initiation and maintenance of tumors. To investigate the correlation between Kras(G12D)-1,011 and mTOR, the inTOR signaling pathway was detected by western blot analysis. We found that Kras(G12D)-LOH up-regulated Alct, AMPK, REDD1 and niTOR in PDAC cells. In summary, our results demonstrated that Krascup-LOH promotes oncogenic Krasinduced PDAC by regulating energy metabolism and mTOR signaling pathway. These data may provide novel therapeutic perspectives for PDAC.