Lu-Hai Wang
China Medical University, Taiwan
Title: Transketolase regulates dynamic switch of glucose metabolism to control breast cancer cell metastasis via α-KG signaling pathway Cancer Cell Metastasis via α-KG Signaling Pathway
Biography
Biography: Lu-Hai Wang
Abstract
Metabolic reprogramming including glucose metabolism is associated with progression of tumor growth. To identify the important players in such reprogramming, we employed 4T1/BALB/c syngeneic model to compare tumors of varying sizes. We identified the glycolytic enzyme transketolase (TKT) to be up-regulated in the bigger tumors. We found TKT expression levels were the highest in lymph node metastases compared with primary tumor and normal tissues of patients. Patients with higher TKT levels had poor overall survival. Reduced TKT attenuated cancer cell growth and metastatic behaviors by in vitro and in vivo assays. Depletion of TKT elevated the expression of alpha-ketoglutarate (α-KG), which was able to inhibit cancer cell growth and metastasis. Reduced TKT or addition of α-KG switched glucose metabolism from glycolysis to TCA cycle through the regulation of enzymes involved in those pathways. These results suggest that TKT-mediated α-KG signaling pathway may be exploited for anti-metastasis therapy in breast cancer.