Figure 6. Schematic representation for the proposed action of MUC4-NIDO domain in disrupting the basement membrane integrity.
Normal pancreatic epithelial cells do not express MUC4; however, in pancreatic cancer, MUC4 is expressed all over the epithelial cells' surface. Through the NIDO domain, the pancreatic cancer-associated MUC4 present in close proximity to the basement membrane, interacts with fibulin-2, and possibly hinders the normal interaction between fibulin-2 and nidogen. Through this interaction MUC4 potentially disrupts the basement membrane integrity by yet undefined non-proteolytic process, as a result of which invasion and metastasis of PC cells is thus mediated by MUC4-NIDO and Fibulin 2 interaction.