Role of lactate dehydrogenase A (LDH-A) in oncogenic transformation: Revisiting a classic glycolytic enzyme.

摘要

Neoplastic cells have a high requirement for glucose as fuel for energy production (ATP) as well as for anabolic activities. In situ studies have also demonstrated that tumor invasiveness, progression, ability to metastasize and overall patient mortality can be predicted based on glucose uptake and lactate production.; This increased production of lactate is due in part to the enzyme lactate dehydrogenase (LDH-A). We have found that decreasing LDH-A activity by siRNA technology results in a decrease in cell proliferation and lactate production of MDA-MB-231 breast adenocarcinomas cells. A pharmacological inhibitor of LDH-A, oxamate, was found to inhibit lactate production, growth of cells in culture and soft agar. However 2D-NMR analysis demonstrates that oxamate may not be a specific LDH-A inhibitor.; Based on these observations we hypothesize that LDH-A is essential for neoplastic glycolysis, growth and transformation and feel that LDH-A as well as oxamate warrant further study as anti-neoplastic importance.