Open AccessLoss of glucose 6-phosphate dehydrogenase function increases oxidative stress and glutaminolysis in metastasizing melanoma cells
Author(s) -
Arin B. Aurora,
Vishal Khivansara,
Ashley Leach,
Jennifer G. Gill,
Misty S. Martin-Sandoval,
Chendong Yang,
Stacy Y. Kasiti,
Divya Bezwada,
Alpaslan Tasdogan,
Wen Gu,
Thomas P. Mathews,
Zhiyu Zhao,
Ralph J. DeBerardinis,
Sean J. Morrison
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2120617119
Subject(s) - pentose phosphate pathway , glutaminolysis , oxidative stress , glucose 6 phosphate dehydrogenase , oxidative phosphorylation , biochemistry , chemistry , malic enzyme , glycolysis , cancer research , dehydrogenase , enzyme , biology
Significance Melanoma metastasis is limited by oxidative stress. Cells that enter the blood experience high levels of reactive oxygen species and usually die of ferroptosis. We found that melanoma cells become more dependent upon the oxidative pentose phosphate pathway to manage oxidative stress during metastasis. When pentose phosphate pathway function was impaired by reduced glucose 6-phosphate dehydrogenase (G6PD ) function, melanoma cells increased malic enzyme activity and glutamine consumption. Melanoma cells thus have redundant and layered protection against oxidative stress.