MST1 suppresses pancreatic cancer progression via ROS induced pyroptosis
Menée à l'aide de lignées cellulaires de cancer du pancréas, d'échantillons tumoraux et d'une xénogreffe sur un modèle murin, cette étude met en évidence un mécanisme par lequel la protéine MST1, via le processus de pyroptose induit par des dérivés réactifs de l'oxygène, supprime la progression tumorale
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease and the incidence is increasing annually. It is critical to reveal and delineate the molecular mechanism promoting PDAC development and progression. Mammalian STE20-like kinase 1 (MST1) is a proapoptotic cytoplasmic kinase and also one of the core components of the Hippo pathway. Here we showed that MST1 was decreased expression in PDAC and restored expression of MST1 promoted PDAC cell death and suppressed the proliferation, migration, invasion and cell spheroid formation of PDAC via caspase-1 induced pyroptosis. Further studies demonstrated that pyroptosis induced by MST1 was independent of Hippo pathway, but mediated by reactive oxygen species (ROS). And ROS scavenger NAC attenuated the activation of caspase-1 induced by MST1 and the effect of MST1 in PDAC cell death, proliferation, migration and invasion. Collectively, our study demonstrated that MST1 suppressed the progression of PDAC cells at least partly through ROS induced pyroptosis. Implications: In this study, we indentified new mechanism of MST1 in inhibiting PDAC development and progression and revealed that MST1 would be a potential prognostic and therapeutic target for PDAC.