Inhibition of ERRα Prevents Mitochondrial Pyruvate Uptake Exposing NADPH-Generating Pathways as Targetable Vulnerabilities in Breast Cancer.

ABSTRACT: Most cancer cells exhibit metabolic flexibility, enabling them to withstand fluctuations in intratumoral concentrations of glucose (and other nutrients) and changes in oxygen availability. While these adaptive responses make it difficult to achieve clinically useful anti-tumor responses when targeting a single metabolic pathway, they can also serve as targetable metabolic vulnerabilities that can be therapeutically exploited. Previously, we demonstrated that inhibition of estrogen-related receptor alpha (ERRα) significantly disrupts mitochondrial metabolism and that this results in substantial antitumor activity in animal models of breast cancer. Here we show that ERRα inhibition interferes with pyruvate entry into mitochondria by inhibiting the expression of mitochondrial pyruvate carrier

SUBMITTER: Park S 

PROVIDER: S-EPMC6604861 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature