| Mucins are high molecular weight glycoproteins, and have grouped into two classes, secreted and membrane-bound. Cancer cells overexpress and/or under-glycosylate transmembrane mucins to exploit their role in cancer progression. The cancer-associated mucins specifically interact with other proteins during the development of various cancers. As these interactions only occur in cancer conditions, and play significant roles in respective cancer progression, these protein-protein interactions might act as potential therapeutic targets. In addition, understanding the mucins' expression profile and their functional role in various preneoplastic and neoplastic conditions will help to know the role of mucins in various cancers' progression.;In this dissertation research, we sought to understand the mechanisms through which the MUC4 mucin promotes pancreatic cancer metastasis. In addition, to understand the role of MUC4 in the progression of other cancers, we investigated its expression and functional association in gastric cancer, where the importance of this mucin was less explored. We have provided experimental evidence that MUC4 interacts with galectin-3 and fibulin-2, thus promoting metastasis. MUC4 interaction with serum galectin-3, whose levels were elevated in pancreatic cancer patients, has a significant role in the adhesion of circulating pancreatic cancer cells to the endothelial cells, an event essential for cancer metastasis. Further, interaction of the MUC4-NIDO domain with fibulin-2, a basement membrane-associated protein, plays a significant role in the invasion of pancreatic cancer cells. As mentioned previously, to investigate the role of MUC4 in gastric cancer progression. We have provided experimental evidence that MUC4 overexpression in gastric cancer cells promotes the aggressiveness of the gastric cancer cells in vitro and in vivo. This may be partly due to MUC4-mediated activation of HER2.;At the same time, we realised the fact that MUC17, a novel membrane-bound mucin, has many functional domains in its primary structure, and its orthologue muc3 has a protective role in the normal colon. We have checked the status of MUC17 expression in normal, pre-neoplastic and neoplastic conditions of human colon. These results indicate that the potential protective effects of this membrane-bound mucin are primarily or secondarily diminished in inflammatory and neoplastic conditions. |
