Our study shows the efficacy of a chronic depletion of Ezrin function, via genetic and pharmacological repression of Ezrin, for blocking EGFR signaling and mitochondrial homeostasis in vitro and in vivo, which could represent an important therapeutic strategy to treat cancers associated with EGFR signaling and/or Ezrin overexpression the most common cause of breast cancer [43, 44]. Here, EGFR is linked to breast cancer.