RRC ID 60137
Author Son SW, Chau GC, Kim ST, Um SH.
Title Vacuolar H+-ATPase Subunit V0C Regulates Aerobic Glycolysis of Esophageal Cancer Cells via PKM2 Signaling.
Journal Cells
Abstract The vacuolar H+-adenosine triphosphatase (ATPase) subunit V0C (ATP6V0C), a proton-conducting, pore-forming subunit of vacuolar ATPase, maintains pH homeostasis and induces organelle acidification. The intracellular and extracellular pH of cancer cells affects their growth; however, the role of ATP6V0C in highly invasive esophageal cancer cells (ECCs) remains unclear. In this study, we examined the role of ATP6V0C in glucose metabolism in ECCs. The ATP6V0C depletion attenuated ECC proliferation, invasion, and suppressed glucose metabolism, as indicated by reduced glucose uptake and decreased lactate and adenosine triphosphate (ATP) production in cells. Consistent with this, expression of glycolytic enzyme and the extracellular acidification rate (ECAR) were also decreased by ATP6V0C knockdown. Mechanistically, ATP6V0C interacted with pyruvate kinase isoform M2 (PKM2), a key regulator of glycolysis in ECCs. The ATP6V0C depletion reduced PKM2 phosphorylation at tyrosine residue 105 (Tyr105), leading to inhibition of nuclear translocation of PKM2. In addition, ATP6V0C was recruited at hypoxia response element (HRE) sites in the lactate dehydrogenase A (LDHA) gene for glycolysis. Thus, our data suggest that ATP6V0C enhances aerobic glycolysis and motility in ECCs.
Volume 8(10)
Published 2019-9-24
DOI 10.3390/cells8101137
PII cells8101137
PMID 31554233
PMC PMC6830105
MeSH Aerobiosis / physiology Carrier Proteins / metabolism* Cell Movement / genetics Cell Proliferation / genetics Cells, Cultured Esophageal Neoplasms / genetics Esophageal Neoplasms / metabolism* Esophageal Neoplasms / pathology* Glycolysis / genetics* HeLa Cells Humans Membrane Proteins / metabolism* Neoplasm Invasiveness Phosphorylation Protein Subunits / physiology Protein Transport / genetics Signal Transduction / genetics Thyroid Hormones / metabolism* Vacuolar Proton-Translocating ATPases / physiology*
IF 5.656
Times Cited 2
Human and Animal Cells TE-8(RCB2098) TE-1(RCB1894)