Hexokinase 2 Is Required for Tumor Initiation and Maintenance and Its Systemic Deletion Is Therapeutic in Mouse Models of Cancer
Menée in vitro et in vivo sur des modèles de cancer du sein et du poumon, cette étude suggère l'intérêt thérapeutique d'une stratégie basée sur l'inhibition de l'hexokinase 2
Accelerated glucose metabolism is a common feature of cancer cells. Hexokinases catalyze the first committed step of glucose metabolism. Hexokinase 2 (HK2) is expressed at high level in cancer cells, but only in a limited number of normal adult tissues. Using Hk2 conditional knockout mice, we showed that HK2 is required for tumor initiation and maintenance in mouse models of KRas-driven lung cancer, and ErbB2-driven breast cancer, despite continued HK1 expression. Similarly, HK2 ablation inhibits the neoplastic phenotype of human lung and breast cancer cells in vitro and in vivo. Systemic Hk2 deletion is therapeutic in mice bearing lung tumors without adverse physiological consequences. Hk2 deletion in lung cancer cells suppressed glucose-derived ribonucleotides and impaired glutamine-derived carbon utilization in anaplerosis. "HK2 deletion exerts resistance to oncogenic transformation "HK2 deletion selectively targets cancer cells "Systemic deletion of HK2 is well tolerated and therapeutic for cancer l "HK2 is required for glucose-derived and glutamine in utilization in anaplerosis