Abstract
Introduction: Tumor cells grow in nutrient and oxygen deprived microenvironments and adapt to the suboptimal growth conditions by altering metabolic pathways. This adaptation process characteristically results in a tumor phenotype that displays upregulated Hif-1α anaerobic glycolysis, chronic acidification, reduced rate of overall protein synthesis, lower rate of cell proliferation and aggressive invasive characteristics. Most transplantable tumors exhibit a pHe of 6.7- 7.0; the DB-1 melanoma xenografts used here have a pHe=6.7. Understanding tumor cell reaction to the microenvironment is a critical factor in predicting the tumor response to radiotherapy. The glucose regulatory molecule, 6-Phosphofructo-2-Kinase/Fructose-2,6- Biphosphatase Isoform-3 (PFKFB3), is a bifunctional enzyme central to glycolytic flux and downstream of the metabolic stress sensor AMP-activated protein kinase (AMPK), which we show activates an isoform of phosphofructokinase (PFK-2).
Radiation Research Society (RRS) 8th Annual Meeting September 25-29, Maui, HI
Recommended Citation
Leeper, D. B.; Mendoza, E. E.; Caro, J.; and Burd, R.
(2010)
"Control of Glycolytic Flux by AMPK and p53-mediated Signaling Pathways in Tumor Cells Grown at Low pH,"
Bodine Journal: Vol. 3:
Iss.
1, Article 20.
DOI: https://doi.org/10.29046/TBJ.003.1.019
Available at:
https://jdc.jefferson.edu/bodinejournal/vol3/iss1/20