THE EFFECT OF MSI1 ON THE EPITHELIAL-MESENCHYMAL TRANSITION IN ADENOCARCINOMA CELLS

The epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell to cell adhesion, detach from the extracellular matrix, and transform into mesenchymal like cells with increased migratory capacity and invasiveness. EMT is of particular concern because it underlies the ability of carcinoma cells to detach from their primary tissue, enter the bloodstream, and invade tissue in other parts of the body. Studies have shown that the Musashi (MSI) family of RNA binding proteins are expressed in stem and cancer cells and are absent in differentiated cells, and that MSI expression is associated with the epithelial state. A human adenocarcinoma alveolar cell line (MDA-MB-231), which displays an epithelial phenotype, was used to investigate whether downregulation of the MSI gene using shRNA would cause the carcinoma cells to gain more mesenchymal-associated properties, such as a loss of cell junctions and adherens proteins. Enzyme-linked immunosorbent assays were used to confirm protein expression and whether the cells were progressing through EMT with the MSI knockdown. The epithelial marker e-cadherin was reduced by 35% in the knockdown cells and the mesenchymal marker Jagged was increased by 16% in the knockdown cells (p<0.05). Cell migration was 35% greater in the knockdown cells than in the control (p< 0.05). These results support MSI’s ability to promote EMT like characteristics when downregulated in this adenocarcinoma cell line. Future experiments to further test this claim include invasion assays and immunohistochemistry staining for EMT-associated proteins.