Investigating the heterogeneity of epithelial-mesenchymal transition in the A549 cell line

Abstract

Non-Small Cell Lung Cancer (NSCLC) is a highly heterogeneous disease characterised by its aggressively metastatic nature. As Epithelial-Mesenchymal Transition (EMT) is the cellular driving mechanism for metastasis, we have exploited the native heterogeneity of the NSCLC cell line, A549, to investigate a range of EMT profiles. We found that the A549 cell line contains subpopulations distinct in EMT gene expression, invasiveness and ability to migrate. We then developed a bioinformatic approach to identify enhancers that were predicted to interact with key EMT genes and from the results, we focused on the EMT transcription factor gene, SNAI1. As SNAI1 demonstrated a range of gene expression levels among our A549 clonal cell lines, using the location of our predicted enhancers within the SNAI1 locus, we investigated DNA methylation and genetic sequence variation. We found that neither the results for DNA methylation or sequence variation in the regions we investigated could explain the variation in SNAI1 gene expression or EMT profile of our A549 clonal cell lines. Indicating that although we have isolated distinct populations from the A549 cell line, other underlying mechanisms are regulating the dynamic range of EMT profiles that we have observed.

Date of Award	2019
Original language	English