ROS mediated EGFR/MEK/ERK/HIF-1α Loop Regulates Glucose metabolism in pancreatic cancer

To investigate the glycometabolism associated mechanism in invasion and metastasis of pancreatic cancer. We screened out genes involved in anaerobic glycolysis headed by HIF-1 alpha,using pre-established a pair of pancreatic cancer cell lines. In this study, we further detected the glucose metabolism state not only in the cells but all also in two groups of patients with different SUVmax on F-18-FDG PET/CT. The data suggests that ROS mediated EGFR/MEK/ERK/HIF-1 alpha loop is activated in high glucose metabolic samples both in vitro and in vivo: The increasing of HIF-1 alpha expression is controlled by activation of EGFR/MEK/ERK pathway in hypoxia condition, HlF-l alpha inhibits excessive release of ROS, the reduction of ROS further activates EGFR to form a positive feedback loop. This difference is closely related to invasion and metastasis capacity of pancreatic cancer, and can be rescued by separate or combined inhibition of EGFR or HIF-l alpha in various degree. These results indicate a new clue to develop therapy of pancreatic cancer by regulating the glucose metabolism. (C) 2018 Elsevier Inc. All rights reserved.