Selected Articles from This Issue Available to Purchase

Epithelial–mesenchymal transition (EMT) is a multistep process underlying the metastatic spread of cancers and the regulation of EMT signaling in different tissues of origin is an active area of research. However, the contribution of epigenetic modifications to EMT signaling is poorly understood. In this study, Miller and colleagues demonstrate a role for lysine-specific demethylase 1 (LSD1), which is overexpressed in colorectal cancer, in regulating EMT signaling via AKT. Colorectal cancer tumors with PIK3CA mutations were shown to be acutely reliant on LSD1 expression but independent of its demethylase activity: in these tumors, LSD1 served as a scaffold to facilitate formation of the CoREST transcriptional repressive complex, which ultimately resulted in AKT-mediated stabilization of the EMT-promoting transcription factor Snail. Concordantly, loss of LSD1 expression via CRISPR/Cas9 or RNAi resulted in proteasomal degradation of Snail and tempering of the migratory phenotype. Taken together, the data support a model in which targeting this...