Study Raises Questions About PDX1 as a Potential Pancreatic Cancer Target
The role of PDX1 in different stages of pancreatic ductal adenocarcinoma is more complex than previously assumed.
A protein thought to fuel pancreatic cancer development may play a much more complicated role than previously recognized. A new study published in Genes and Development has found that PDX1, a transcription factor critical for pancreatic development, has distinct roles at different stages of pancreatic cancer. Researchers report that PDX1 helps keep cancer at bay in normal cells, then eventually contributes to the cancer's growth once a tumor forms.1
Investigators report that there appears to be distinct roles of PDX1 at different stages of pancreatic ductal adenocarcinoma (PDA). They caution that therapeutic approaches against this potential target need to account for PDX1's changing functions at different stages of carcinogenesis.
Researchers from Michigan Medicine and the University of California, San Francisco used mouse models to look at normal pancreas cells, a type of precancerous pancreas lesion called PanIN, and pancreatic cancer cells. In the normal cells, PDX1 maintains the cells' identity as pancreas cells and epithelial cells. However, researchers report that once cells become malignant, PDX1 takes on a new role and contributes to the cancer's growth.
The researchers looked at subtypes of pancreatic cancer and found the lowest levels of PDX1 were actually in the most aggressive cancers. The patients whose tumors had no PDX1 had the worst outcomes. The findings question whether it is a good idea to target PDX1.
1. Roy N, Takeuchi KK, Ruggeri JM, et al. PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance. Genes Dev. 2016 Dec 15; 30(24):2669-2683. doi: 10.1101/gad.291021.116