Nikita Bhalerao, Asmi Chakraborty, Michael P Marciel, Jihye Hwang, Colleen M Britain, Austin D Silva, Isam E Eltoum, Robert B Jones, Katie L Alexander, Lesley E Smythies, Phillip D Smith, David K Crossman, Michael R Crowley, Boyoung Shin, Laurie E Harrington, Zhaoqi Yan, Maigen M Bethea, Chad S Hunter, Christopher A Klug, Donald J Buchsbaum, Susan L Bellis
The role of aberrant glycosylation in pancreatic ductal adenocarcinoma (PDAC) remains an under-investigated area of research. In this study, we determined that the ST6GAL1 sialyltransferase, which adds α2,6-linked sialic acids to N-glycosylated proteins, is upregulated in patients with early-stage PDAC, and further increased in advanced disease. A tumor-promoting function for ST6GAL1 was elucidated using tumor xenograft experiments with human PDAC cells. Additionally, we developed a genetically-engineered mouse (GEM) with transgenic expression of ST6GAL1 in the pancreas, and found that mice with dual expression of ST6GAL1 and oncogenic KRASG12D have greatly accelerated PDAC progression compared with mice expressing KRASG12D alone...
August 29, 2023: JCI Insight