Metabolic reprogramming in breast cancer results in distinct mitochondrial bioenergetics between luminal and basal subtypes.

Mitochondrial dysfunction is a key feature of cancer and frequently associated with an increased aggressiveness and metastatic potential. Recent evidence highlights the metabolic re-wiring that takes place during the epithelial to mesenchymal transition (EMT), a process that drives the invasive capability of malignant tumors, and proposes a mechanistic link between mitochondrial dysfunction and EMT that has been only partially investigated. In the present study, we characterized mitochondrial function and bioenergetic status of cultured human breast cancer cell lines, luminal-like, and basal-like subtypes. Trough the combination of biochemical and functional studies, we demonstrated that basal-like cell lines exhibit impaired, but not completely inactive, mitochondrial function, and rely on a consequent metabolic switch to glycolysis to support their ATP demand. These altered metabolic activities are linked to modifications of key electron transport chain proteins with a significant increase of ROS levels compared to luminal cells. Furthermore, we observed that the stable knockdown of EMT markers cause mitochondria functional changes that impact on the metabolic status of cancer cells that acquire a hybrid glycolysis/OXPHOS phenotype to sustain their metabolic demand.