Lamin A/C-EZH2 interaction in modulating Epithelial-to-mesenchymal Transistion in breast cancer cells
Epithelial-to-mesenchymal transition (EMT) is a developmentally conserved cell biological program adopted by cancer cells to metastasize to different organs. In this process, compact, cobblestone-shaped epithelial cells transform into more slender-shaped mesenchymal cells. Throughout metastasis, cells reside at various stages along the E-M spectrum. Epithelial cells are not necessarily converted to mesenchymal cells, as cells in the E-M continuum exhibit greater survival advantages and better metastatic ability than complete mesenchymal forms. During metastasis, epithelial cells traverse through narrow capillaries, inducing nucleus rupture. The nucleus is protected by type V intermediate filament proteins, Lamins, in the inner nuclear membrane, providing structural integrity, facilitating genome organization, and acting as an impediment to cell migration. Therefore, Lamin expression is downregulated to facilitate nuclear compliance during EMT, serving as a precursor for metastasis. Here, we aim to address the mechanism of Lamin downmodulation and its role in genome organization during EMT. We have attempted to address these questions in three independent and well-established breast cancer cell lines representing cells at specific stages of the EM spectrum, providing a paradigm to elucidate the role of Lamins in genome organization and function during EMT. Overall design: RNA-Seq profiling of MCF10A cells upon Lamin A/C knockdown. siRNA for Lamin A/C was used and control non-targeting LacZ was used.