Environmental cystine drives glutamine anaplerosis and sensitizes cancer cells to glutaminase inhibition.

ABSTRACT: Many mammalian cancer cell lines depend on glutamine as a major tri-carboxylic acid (TCA) cycle anaplerotic substrate to support proliferation. However, some cell lines that depend on glutamine anaplerosis in culture rely less on glutamine catabolism to proliferate in vivo. We sought to understand the environmental differences that cause differential dependence on glutamine for anaplerosis. We find that cells cultured in adult bovine serum, which better reflects nutrients available to cells in vivo, exhibit decreased glutamine catabolism and reduced reliance on glutamine anaplerosis compared to cells cultured in standard tissue culture conditions. We find that levels of a single nutrient, cystine, accounts for the differential dependence on glutamine in these different environmental contex

SUBMITTER: Muir A 

PROVIDER: S-EPMC5589418 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature