RESUMO
Cell migration is crucial for cancer dissemination. We find that AMP-activated protein kinase (AMPK) controls cell migration by acting as an adhesion sensing molecular hub. In 3-dimensional matrices, fast-migrating amoeboid cancer cells exert low adhesion/low traction linked to low ATP/AMP, leading to AMPK activation. In turn, AMPK plays a dual role controlling mitochondrial dynamics and cytoskeletal remodelling. High AMPK activity in low adhering migratory cells, induces mitochondrial fission, resulting in lower oxidative phosphorylation and lower mitochondrial ATP. Concurrently, AMPK inactivates Myosin Phosphatase, increasing Myosin II-dependent amoeboid migration. Reducing adhesion or mitochondrial fusion or activating AMPK induces efficient rounded-amoeboid migration. AMPK inhibition suppresses metastatic potential of amoeboid cancer cells in vivo, while a mitochondrial/AMPK-driven switch is observed in regions of human tumours where amoeboid cells are disseminating. We unveil how mitochondrial dynamics control cell migration and suggest that AMPK is a mechano-metabolic sensor linking energetics and the cytoskeleton.
Assuntos
Proteínas Quinases Ativadas por AMP , Dinâmica Mitocondrial , Neoplasias , Humanos , Trifosfato de Adenosina/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Adesão Celular , Movimento Celular/fisiologia , Miosina Tipo II/metabolismo , Fosforilação Oxidativa , FosforilaçãoRESUMO
Yolk sac tumors are most common tumors among the germ cell tumors (GCTs) in children, mostly involving the gonads. But yolk sac tumors involving the vagina are very rare. These usually present with per vaginal bleeding and vaginal mass. Presentation with discharged tumor fragments is very unusual. We present a rare case of yolk sac tumor of vagina in an infant with very unusual presentation of per vaginal tumor tissue discharge, histopathological examination of which was diagnostic.