MST1 Suppresses Pancreatic Cancer Progression via ROS-Induced Pyroptosis

Molecular Cancer Research : MCR
Jiujie CuiMing Quan

Abstract

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.

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Citations

Sep 11, 2019·Cell Death & Disease·Xiaojing XiaJianhe Hu
Oct 22, 2019·European Journal of Immunology·Andrea CossarizzaArturo Zychlinsky
Jul 2, 2020·Journal of Experimental & Clinical Cancer Research : CR·Jia-Zhou LiuWan-Jiang Xue
Mar 16, 2021·Frontiers in Oncology·Lei WangPengfei Ge
Mar 30, 2021·Signal Transduction and Targeted Therapy·Pian YuXiang Chen
May 5, 2021·Journal of Experimental & Clinical Cancer Research : CR·Yixin TanMei Yi
Aug 1, 2021·Nature Reviews. Gastroenterology & Hepatology·Xin ChenDaolin Tang
Aug 13, 2021·Frontiers in Oncology·Dengqiang WuSufang Zhou
Nov 2, 2021·Frontiers in Cell and Developmental Biology·Xiaocui Zhang, Qing Yang
Jan 23, 2022·Apoptosis : an International Journal on Programmed Cell Death·Ying HuangGuo Wang

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