Authors:
Andrew D. James, Anthony Chan, Oihane Erice Azparren, Ajith K Siriwardena, and Jason IE Bruce
Summary:
Pancreatic cancer is an aggressive cancer with poor prognosis and limited treatment options. Cancer cells rapidly proliferate and are resistant to cell death due, in part, to a shift from mitochondrial metabolism to glycolysis. We hypothesised that this shift is important in regulating cytosolic Ca2+ ([Ca2+]i), since the ATP-dependent plasma membrane Ca2+ ATPase (PMCA) is critical for maintaining low [Ca2+]i and thus cell survival. The present study aimed to determine the relative contribution of mitochondrial vs glycolytic ATP in fuelling the PMCA in human pancreatic cancer cells. We report that glycolytic inhibition induced profound ATP depletion, PMCA inhibition, [Ca2+]i overload and cell death in PANC1 and MIA PaCa-2 cells. Conversely, inhibition of mitochondrial metabolism had no effect, suggesting that glycolytic ATP is critical for [Ca2+]i homeostasis and thus survival. Targeting the glycolytic regulation of the PMCA may therefore be an effective strategy for selectively killing pancreatic cancer, whilst sparing healthy cells.
Source:
The Journal of Biological Chemistry; (10/24/13)