Protein kinase CK2-dependent aerobic glycolysis-induced lactate dehydrogenase A enhances the migration and invasion of cancer cells

Dae Kyun Im, Heesun Cheong, Jong Suk Lee, Min-Kyu Oh, Kyung Mi Yang

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Abstract

We investigated the intracellular metabolic fluxes of protein kinase CK2-activating (Cα OE) cells and role of lactate dehydrogenase A (LDHA) as a contributor of tumorigenesis after reprogrammed glucose metabolism. Facilitated aerobic glycolysis was confirmed via isotope tracer analysis, in which 13 C 6 -Glc or 13 C 5 -Gln was added to the media, following which metabolites converted from Cα OE cells were identified. We found a greater decrease in cell survival, colony-forming ability, migration, and Cα OE cell invasion under glucose (Glc)-depletion conditions than under glutamine (Gln)-depletion conditions. Cancer cell migration and invasion increased due to LDHA elevation of the altered metabolic axis driven by activated CK2. FX11 treatment and LDHA knockdown suppressed migration and invasion through ROS generation, but this was partially reversed by the antioxidant N-acetylcysteine (NAC). Moreover, LDHA inhibition decreased tumor growth in a mouse xenograft model transplanted with Cα OE cells. Finally, we concluded that LDHA is an excellent metabolic target for tumor therapy, based on CK2α derived aerobic glycolysis.

Original languageEnglish
Article number5337
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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