Targeting Energy Metabolic Pathways as Therapeutic Intervention for Breast Cancer.

摘要

During the past grant period, we obtained further evidence that eukaryotic elongation factor-2 kinase (eEF-2K) plays an important role in the development and progression of cancer by regulating cellular metabolism. In the study of the molecular mechanisms and pathways by which eEF-2K promotes glycolysis, we demonstrated that c-Myc-PKM2 pathway mediated the effect of eEF- 2K on glycolysis. We further showed that suppression of eEF-2K impeded the induction of glycolysis in tumor cells subjected to hypoxia, enhanced apoptosis, and sensitized breast cancer cells to hypoxic insult. The results obtained during the last grant period have identified eEF-2K as a critical regulator of cell proliferation by promoting cancer cell metabolism, and provide new evidence that the effect of eEF- 2K on glycolysis is mediated through PKM2 and c-Myc. In addition, depletion of eEF-2K prevented the hypoxia-induced glycolysis and enhanced the sensitivity of tumor cells to hypoxic stress. These results underscore the potential of eEF-2K as a target for prevention and treatment of breast cancer.