Phosphoenolpyruvate Carboxykinase Maintains Glycolysis-driven Growth in Drosophila Tumors

dc.contributor.author Hussain, Rashid
dc.contributor.author Shaukat, Zeeshan
dc.contributor.author Khan, Mahwish
dc.contributor.author Saint, Robert
dc.contributor.author Gregory, Stephen L
dc.date.accessioned 2017-10-04T23:48:57Z
dc.date.available 2017-10-04T23:48:57Z
dc.date.issued 2017-09-14
dc.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/. en
dc.description.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. en
dc.identifier.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. en
dc.identifier.doi https://doi.org/10.1038/s41598-017-11613-2 en
dc.identifier.issn 2045-2322
dc.identifier.uri http://hdl.handle.net/2328/37519
dc.language.iso en
dc.oaire.license.condition.license CC-BY
dc.publisher Nature Publishing Group en
dc.relation http://purl.org/au-research/grants/nhmrc/1087308 en
dc.relation.grantnumber NHMRC/1087308
dc.rights © The Author(s) 2017 en
dc.rights.holder The Author(s) en
dc.subject Mechanisms of disease en
dc.subject Cancer metabolism en
dc.subject Genomic instability en
dc.title Phosphoenolpyruvate Carboxykinase Maintains Glycolysis-driven Growth in Drosophila Tumors en
dc.type Article en
local.contributor.authorOrcidLookup Gregory, Stephen: https://orcid.org/0000-0002-0046-5815 en_US
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