HPV18 E6 inhibits & alpha;-ketoglutarate-induced pyroptosis of esophageal squamous cell carcinoma cells via the P53/MDH1/ROS/GSDMC pathway

Oncogene E6 plays a critical role in the development and progression of esophageal cancer caused by human papillomavirus (HPV) infection. Alpha-ketoglutarate (AKG) is a key metabolite in the tricarboxylic acid cycle and has been widely used as a dietary and anti-ageing supplement. In this study, we found that treating esophageal squamous carcinoma cells with a high dose of AKG can induce cell pyroptosis. Furthermore, our research confirms that HPV18 E6 inhibits AKG-induced pyroptosis of esophageal squamous carcinoma cells by lowering P53 expression. P53 downregulates malate dehydrogenase 1 (MDH1) expression; however, MDH1 downregulates L-2-hydroxyglutarate (L-2HG) expression, which inhibits a rise in reactive oxygen species (ROS) levels-as L-2HG is responsible for excessive ROS. This study reveals the actuating mechanism behind cell pyroptosis of esophageal squamous carcinoma cells induced by high concentrations of AKG, and we posit the molecular pathway via which the HPV E6 oncoprotein inhibits cell pyroptosis.

Automated summary

This study reveals that alpha-ketoglutarate (AKG) can induce cell pyroptosis in esophageal squamous carcinoma cells, while HPV18 E6 inhibits AKG-induced pyroptosis by decreasing P53 expression. The study provides insights into the mechanism of cell pyroptosis induced by high concentrations of AKG and the molecular pathway through which HPV E6 oncoprotein inhibits this process.