ALDH1L2 regulates reactive oxygen species and acinar-to-ductal metaplasia in the pancreas - PubMed
19 hours ago
- #Pancreatic Cancer
- #ALDH1L2
- #Acinar-to-Ductal Metaplasia
- ALDH1L2 is a mitochondrial enzyme that produces NADPH and regulates reactive oxygen species (ROS) and formate levels in pancreatic acinar cells.
- ALDH1L2 expression decreases during acinar-to-ductal metaplasia (ADM) and is absent in ductal cells; its loss elevates ROS, promotes ADM in pancreatitis, and accelerates tumor progression in pancreatic cancer models.
- Increased ROS driven by ALDH1L2 loss is identified as a driver of ADM, and elevated circulating formate may serve as a biomarker for pancreatic ductal adenocarcinoma (PDAC) progression.
- Persistent ADM combined with KRAS mutation leads to precancerous PanIN and can progress to PDAC, with metabolic changes during early ADM events being poorly understood.