Glucose-6-Phosphate Dehydrogenase Is Not Essential for K-Ras-Driven Tumor Growth or Metastasis

Citation:

Ghergurovich, Jonathan M, et al. “Glucose-6-Phosphate Dehydrogenase Is Not Essential for K-Ras-Driven Tumor Growth or Metastasis”. Cancer Res 80.18 (2020): , 80, 18, 3820-3829. Web.

Date Published:

2020 09 15

ISSN:

1538-7445

Abstract:

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. SIGNIFICANCE: K-Ras-driven tumors can grow and metastasize even in the absence of the oxidative pentose pathway, a main NADPH production route.

DOI:

10.1158/0008-5472.CAN-19-2486

Alternate Journal:

Cancer Res