Reductive carboxylation mediated oxidative stress defense supports anchorage independent cell growth

Background Cancer cells consume large amount of glutamine for growth and proliferation. In normal mitochondria, glutamine is converted to a-ketoglutarate, which is further oxidized through the TCA cycle [1]. Recent studies find that under certain extreme conditions, such as mitochondria dysfunction and hypoxia, cells use glutamine through reductive carboxylation (RC) to generate acetyl-CoA for lipogenesis. During tumor development, the acquisition of anchorage independence enables cancer cells to survive without their natural extracellular matrix, but this comes at the price of increased oxidative stress [2]. Here we examined reprogramming of glutamine metabolism during adaptation to growth of anchorage independent tumor spheroids, including reprogramming of pathways that counteract production of reactive oxygen species (ROS).