MST1 Suppresses Pancreatic Cancer Progression via ROS-Induced Pyroptosis

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, and its 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...

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Bibliographic Details
Published in:Molecular cancer research 2019-06, Vol.17 (6), p.1316-1325
Main Authors: Cui, Jiujie, Zhou, Zhuqing, Yang, Haiyan, Jiao, Feng, Li, Ning, Gao, Yong, Wang, Liwei, Chen, Jingde, Quan, Ming
Format: Article
Language:English
Subjects:
Animals
Apoptosis - physiology
Carcinoma, Pancreatic Ductal - metabolism
Carcinoma, Pancreatic Ductal - pathology
Cell Line, Tumor
Cell Movement - physiology
Cell Proliferation - physiology
Disease Progression
Female
Gene Expression Regulation, Neoplastic - physiology
Hepatocyte Growth Factor
Humans
Intracellular Signaling Peptides and Proteins
Mice
Mice, Nude
Pancreas - metabolism
Pancreas - pathology
Pancreatic Neoplasms
Pancreatic Neoplasms - metabolism
Pancreatic Neoplasms - pathology
Prognosis
Protein Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins
Pyroptosis - physiology
Reactive Oxygen Species - metabolism
Signal Transduction - physiology
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Summary:Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, and its 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 expression was decreased 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 the Hippo pathway, but mediated by reactive oxygen species (ROS). And ROS scavenger N-acetyl-cysteine 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 identified a new mechanism of MST1 in inhibiting PDAC development and progression and revealed that MST1 would be a potential prognostic and therapeutic target for PDAC.
ISSN:1541-7786
1557-3125
DOI:10.1158/1541-7786.mcr-18-0910