Bodine Journal

Article Title

Control of Glycolytic Flux by AMPK and p53-mediated Signaling Pathways in Tumor Cells Grown at Low pH

Authors

D. B. Leeper, Thomas Jefferson UniversityFollow
E. E. Mendoza, University of ArizonaFollow
J. Caro, Thomas Jefferson UniversityFollow
R. Burd, University of ArizonaFollow

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