An investigation into the role of Lamin A in cell motility and Epithelial to Mesenchymal Transition in Colorectal Cancer

Abstract

The Lamin A protein has a number of structural and gene-regulatory roles. Recently novel functions for Lamin A have been established in colorectal cancer, where expression of Lamin A is a biomarker of poor patient prognosis. Colorectal cancer is the fourth most frequent cause of cancer-related death world-wide, therefore understanding the molecular mechanisms behind the disease is of importance in the development of future therapeutic strategies to reduce mortality rates. SW480 colorectal cancer cells that artificially express Lamin A (SW480/Lamin A cells) demonstrate increased cell motility and a mesenchymal-like morphology, suggesting a more aggressive cancer cell phenotype in the presence of Lamin A expression. The aims of this project were to further explore how Lamin A expression contributes to a more aggressive cancer cell phenotype in SW480 cells. Herein cell density experiments show that at low cell density, SW480/Lamin A cells express the mesenchymal markers Slug and Vimentin. Scratch wounding assays of SW480/Lamin A cells show that cell junctions are absent from these cells at high cell density and the cytoskeletons of SW480/Lamin A cells are able to form motile structures. Finally silencing of Lamin A in SW480/Lamin A cells caused some of these changes to reversed. Together this data indicate that transfection of SW480 cells with Lamin A permits a signalling environment conducive to EMT and thus patients with high levels of Lamin A in the cells in their tumours may have a poorer prognosis due to increased cellular metastatic potential as a result of EMT.