Metabolic Control of Breast Cancer Metastasis
Micrometastatic cells display increased mitochondrial oxidative phosphorylation
Oxidative phosphorylation is critical for lung metastasis
OXPHOS may promote metastatic seeding in several ways. Increased ATP generation through OXPHOS may provide energy for cytoskeleton remodeling for motility or to survive anoikis during cell detachment and migration. Increased ROS production through OXPHOS may promote cell motility by activating oncogenic signaling, as mitochondrial ROS‐inducing mutations are sufficient to trigger metastasis. Epidemiological data in humans also support a role for OXPHOS in cancer progression, showing that treatment with the diabetes drug metformin (complex I inhibitor) is protective against the relapse and metastasis of breast cancer. We are excited to explore these possibilities in future projects in the lab, including studies that define which specific steps of the metastatic cascade OXPHOS is critical for to determine when it might be applied for clinical benefit against metastasis.