@article{ce8c439256c34423a8e4a10faa7b5c8e,
title = "Upregulation of Antioxidant Capacity and Nucleotide Precursor Availability Suffices for Oncogenic Transformation",
abstract = "The basic elements required for oncogenic transformation remain undefined. By analyzing glucose-6-phosphate dehydrogenase (G6PD)-mediated oncogenic transformation, Zhang et al. show that upregulation of antioxidant defense and nucleotide production suffices to transform murine and human cells. Therefore, oncogenic transformation may involve overcoming a limited redox balance capacity and nucleotide precursor availability.",
keywords = "G6PD, NAD kinase, NADPH, antioxidants, cancer metabolism, nucleosides, nucleotide synthesis, oncogenic transformation, pentose phosphate pathway, redox regulation",
author = "Yang Zhang and Yi Xu and Wenyun Lu and Ghergurovich, {Jonathan M.} and Lili Guo and Blair, {Ian A.} and Rabinowitz, {Joshua D.} and Xiaolu Yang",
note = "Funding Information: We thank R. Weinberg for PHMLEB cells, and D. Harischandra, S. Ghaisas, S. Yu, L. Huang, A. Mancuso, and W. Prall for technical assistance. This study was supported by NIH grants R01CA182675, R01CA184867, R01CA235760, R01CA243520, and R50CA211437. Y.Z. performed most experiments. Y.X. helped with animal studies and some other experiments. W.L. and J.M.G. performed and J.D.R. supervised the metabolomics study, LC-HRMS-based NADPH measurement, and in vivo NAD+-NADP+ flux analysis. L.G. performed and I.A.B. supervised the focused metabolite analysis by LC-MS. J.D.R. suggested the G6PD-NADK connection. X.Y. conceived and supervised the project. X.Y. and Y.Z. designed the research plan, analyzed the data, and wrote the manuscript with major inputs from J.D.R. All authors reviewed the manuscript. J.D.R. is a paid consultant of Pfizer; a founder, director, and stockholder of Farber Partners; a founder and stockholder in Toran Therapeutics; inventor of patents in the area of G6PD and NADPH metabolism held by Princeton University; and a director of the Princeton University-PKU Shenzhen collaboration. I.A.B. is a founder of Proteoform Bio and a paid consultant for Calico, Chimerix, PTC Therapeutics, Takeda Pharmaceuticals, Vivo Capital, and Scitemex LLC. Funding Information: We thank R. Weinberg for PHMLEB cells, and D. Harischandra, S. Ghaisas, S. Yu, L. Huang, A. Mancuso, and W. Prall for technical assistance. This study was supported by NIH grants R01CA182675 , R01CA184867 , R01CA235760 , R01CA243520 , and R50CA211437 . Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = jan,
day = "5",
doi = "10.1016/j.cmet.2020.10.002",
language = "English (US)",
volume = "33",
pages = "94--109.e8",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "1",
}