In this model, we report that Cox7b, a structural subunit of ETC Complex IV [51,52], drives metastatic breast cancer cell homing to the brain: repression of Cox7b expression selectively blocked the migration of brain-seeking variants towards astrocytes and their capacity to generate brain metastases in mice; conversely, pan-metastatic parental cells manipulated to gain Cox7b expression increased their selective migration towards astrocytes and their capability to generate brain metastases. Here, COX7B is linked to breast carcinoma.