Regulome of cancer epithelial-mesenchymal transition (EMT)

Abstract

During metastasis, cancer cells employ autophagy to meet elevated energy demands, of which the adaptor protein 14-3-3γ may play a role in this autophagic mechanism. It is hypothesized that 14-3-3γ activity promotes autophagy and EMT, and inhibition of 14-3-3γ may lead to the prevention of metastasis by suppressing EMT genes or starving the cancer cells of nutrients through autophagy suppression. To elucidate any differentially expressed genes (DEGs) after EMT induction that are involved in autophagy and may potentially be 14-3-3 protein targets, RNA-Seq was carried out and a pipeline was established to determine the differences in expression of the genes regulated directly or indirectly through 14-3-3γ interaction with transcription factors or repressors. A number of genes that are known to play various roles in autophagy were found to be differentially expressed after treatment with DMOG and TGFβ, which suggests a correlation between autophagy and metastasis. These genes are predicted to interact with 14-3-3 proteins, which suggests 14-3-3γ may have a significant role in regulating autophagy and metastasis, thereby contributing to cancer progression.