Glucose-6-phosphate dehydrogenase is not essential for K-ras-driven tumor growth or metastasis

Jonathan M. Ghergurovich, Mark Esposito, Zihong Chen, Joshua Z. Wang, Vrushank Bhatt, Taijin Lan, Eileen White, Yibin Kang, Jessie Yanxiang Guo, Joshua D. Rabinowitz

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


The enzyme glucose-6-phosphate dehydrogenase (G6PD) is a major contributor to NADPH production and redox homeostasis and its expression is upregulated and correlated with negative patient outcomes in multiple human cancer types. Despite these associations, whether G6PD is essential for tumor initiation, growth, or metastasis remains unclear. Here, we employ modern genetic tools to evaluate the role of G6PD in lung, breast, and colon cancer driven by oncogenic K-Ras. Human HCT116 colorectal cancer cells lacking G6PD exhibited metabolic indicators of oxidative stress, but developed into subcutaneous xenografts with growth comparable with that of wild-type controls. In a genetically engineered mouse model of non-small cell lung cancer driven by K-Ras G12D and p53 deficiency, G6PD knockout did not block formation or proliferation of primary lung tumors. In MDA-MB-231-derived human triple-negative breast cancer cells implanted as orthotopic xenografts, loss of G6PD modestly decreased primary site growth without ablating spontaneous metastasis to the lung and moderately impaired the ability of breast cancer cells to colonize the lung when delivered via tail vein injection. Thus, in the studied K-Ras tumor models, G6PD was not strictly essential for tumorigenesis and at most modestly promoted disease progression.

Original languageEnglish (US)
Pages (from-to)3820-3829
Number of pages10
JournalCancer Research
Issue number18
StatePublished - Sep 15 2020

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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