Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA.

ABSTRACT: Although lactic acidosis is a prominent feature of solid tumors, we still have limited understanding of the mechanisms by which lactic acidosis influences metabolic phenotypes of cancer cells. We compared global transcriptional responses of breast cancer cells in response to three distinct tumor microenvironmental stresses: lactic acidosis, glucose deprivation, and hypoxia. We found that lactic acidosis and glucose deprivation trigger highly similar transcriptional responses, each inducing features of starvation response. In contrast to their comparable effects on gene expression, lactic acidosis and glucose deprivation have opposing effects on glucose uptake. This divergence of metabolic responses in the context of highly similar transcriptional responses allows the identification of a sm

SUBMITTER: Chen JL 

PROVIDER: S-EPMC2937306 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature