Doctor of Philosophy (PhD)
Biochemistry & Molecular Biology
Surinder K. Batra
MUC1 is overexpressed in over 90% of pancreatic cancer cases, and its interaction with beta-catenin promotes progression of the disease. Various in vitro and in vivo methods show that beta-catenin and MUC1 interact by way of the cytoplasmic tail of MUC1 (MUC1.CT). This interaction occurs in the membrane of pancreatic cancer cells but is found to a smaller extent in the nucleus as well. Biophysical methods suggest that MUC1 interacts with beta-catenin through a sequence of amino acids in the tail of MUC1 that sit very near the transmembrane domain of MUC1. In pancreatic ductal adenocarcinoma cells, it appears that EGF stimulation causes tyrosine residue phosphorylation of the cytoplasmic tail of MUC1 and a simultaneous reduction in the beta-catenin/MUC1.CT interaction in the membrane of the cells. The evidence presented here indicates that phosphorylation of the tail of MUC1 tends to decrease its interaction with beta-catenin.
While studying the beta-catenin/MUC1.CT interaction, it was inadvertently discovered that a Met receptor inhibitor, SU11274, fluoresces when excited by laser light of 488 nm. The inhibitor moves rapidly into cells and accumulates in discrete regions of the cell. Evidence suggests that SU11274 associates with the endoplasmic reticulum.
Wiest, Edwin, "The Beta-Catenin/MUC1.CT Interaction in Pancreatic Cancer" (2018). Theses & Dissertations. 270.