Internalization of Extracellular ATP in Cancer Cells and Development of New Generations of Anticancer Glucose Transport Inhibitors
Year: 2014
Type: article
Abstract: The past decade has witnessed remarkable progress toward understanding the reprogrammed metabolism in cancer, an emerging hallmark as well as an active area of basic, translational, and clinical research.About ninety years ago, Otto Warburg pioneered quantitative investigations of cancer metabolism and discovered that cancer cells exhibit a phenotype of increased glycolysis even under aerobic conditions, known as the Warburg effect.Warburg speculated that the reason for the upregulated glycolysis was for compensating the ATP shortage due to dysfunctions of mitochondria in cancer cells.Despite subsequent progresses, the biological reasons for ATP synthesis by aerobic glycolysis in cancer cells are only partially understood.Intriguingly, intratumoral (extracellular) ATP levels are 10 3 to 10 4 times higher than those in normal tissues.We showed that although extracellular ATP is not known to cross the plasma membrane by itself, extracellular ATP in the range of the intratumoral ATP levels induced large intracellular ATP concentration increase in A549 human lung cancer cells and promoted cancer cell survival.More importantly, we reported that a nonhydrolyzable fluorescent ATP was internalized by A549 cells through macropinocytosis as visualized by fluorescence microscopy.The induced ATP increase was reduced by the macropinocytosis inhibitor EIPA but persisted even when mitochondrial oxidative Fellowship, 2013 Student Enhancement Award, 2013 Graduate Student Senate Original
Author: Yanrong Qian
Institution: Ohio University
Language: English
Subfield: Physiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2338982440