GSE171444
MLL3 loss drives metastasis and therapeutic resistance by promoting a hybrid EMT state [RNA-seq]
Loss of MLL3 facilitates mesenchymal cells to acquire a mesenchymal/epithelial hybrid state during metastatic colonization. The MET occurring in distant metastases is likely driven by stromal signals in the metastatic niche. One signaling pathway that promotes the MET is the activation of protein kinase A (PKA). The MET hybrid cells can be identified as CD44+CD104+/high. Forskolin treatment generated significantly more CD44+CD104high hybrid cells in MLL3-mutant cells than the WT MDA-MB-231 cells. While both WT and MLL3-mutant CD44+CD104high hybrid EMT cells showed significantly increased lung metastatic ability than the counterpart CD44+CD104low mesenchymal cells, the MLL3-mutant hybrid cells showed a much greater metastasis-initiating ability than the WT hybrid cells. Here we reported the gene expression profiles of CD44+CD104high E/M hybird and CD44+CD104-/low mesenchymal cell populations sorted from Foskolin-treated, MLL3-null MDA-MB-231 cells. Overall design: We treated the WT and MLL3-mutant MDA-MB-231 cells with the PKA activator forskolin for 14 days and used flow cytometry to isolate CD44+CD104high hybrid EMT and CD44+CD104low mesenchymal tumor cells. RNA was isolated from these populations and RNA-seq was preformed for comparison the gene expression.