Phosphoenolpyruvate Carboxykinase Maintains Glycolysis-driven Growth in Drosophila Tumors
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Date
2017-09-14
Authors
Hussain, Rashid
Shaukat, Zeeshan
Khan, Mahwish
Saint, Robert
Gregory, Stephen L
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
Rights
© The Author(s) 2017
Rights Holder
The Author(s)
Abstract
Tumors frequently fail to pass on all their chromosomes correctly during cell division, and this chromosomal instability (CIN) causes irregular aneuploidy and oxidative stress in cancer cells. Our objective was to test knockdowns of metabolic enzymes in Drosophila to find interventions that could exploit the differences between normal and CIN cells to block CIN tumor growth without harming the host animal. We found that depleting by RNAi or feeding the host inhibitors against phosphoenolpyruvate carboxykinase (PEPCK) was able to block the growth of CIN tissue in a brat tumor explant model. Increasing NAD+ or oxidising cytoplasmic NADH was able to rescue the growth of PEPCK depleted tumors, suggesting a problem in clearing cytoplasmic NADH. Consistent with this, blocking the glycerol-3-phosphate shuttle blocked tumor growth, as well as lowering ROS levels. This work suggests that proliferating CIN cells are particularly vulnerable to inhibition of PEPCK, or its metabolic network, because of their compromised redox status.
Description
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Keywords
Mechanisms of disease, Cancer metabolism, Genomic instability
Citation
Hussain, R., Shaukat, Z., Khan, M., Saint, R., & Gregory, S. L. (2017). Phosphoenolpyruvate Carboxykinase Maintains Glycolysis-driven Growth in Drosophila Tumors. Scientific Reports, 7.