RANK rewires energy homeostasis in lung cancer cells and drives primary lung cancer

摘要: Lung cancer is the leading cause of deaths. Besides smoking, epidemiological studies have linked female sex hormones to lung in women; however, underlying mechanisms remain unclear. Here we report that receptor activator nuclear factor-kB (RANK), key regulator osteoclastogenesis, frequently expressed primary tumors, an active RANK pathway correlates with decreased survival, and pharmacologic inhibition reduces tumor growth patient-derived xenografts. Clonal genetic inactivation KRasG12D mouse epithelial cells markedly impairs progression -driven cancer, resulting a significant survival advantage. Mechanistically, rewires energy homeostasis human murine promotes expansion stem-like cells, which blocked by inhibiting mitochondrial respiration. Our data also indicate differences between male mice, show can promote via pathway. These uncover direct role for may explain why accelerate development. Inhibition using approved drug denosumab be therapeutic candidate cancer.