PCAF, ISX, and BRD4: a maleficent alliance serving lung cancer malignancy.

Tumor progression and malignancy are frequently associated with aberrant activation of epithelial-mesenchymal transition (EMT), which orchestrates dramatic changes in gene expression, involving genetic and epigenetic regulation. External stimuli generated by tumor-stroma interactions need to be adequately processed to specifically alter expression of key EMT transcription factors and associated genes. In this issue of EMBO Reports, Wang and colleagues demonstrate how epigenetic modifiers are utilized to induce EMT and metastasis [1]. Acetylation of intestine-specific homeobox (ISX) by p300/CBP-associated factor (PCAF) induces a cascade that results in Snail and Twist activation through histone modifications by a novel complex of PCAF, ISX, and bromodomain-containing protein 4 (BRD4). These findings open novel possibilities of therapeutic intervention to inhibit EMT and metastasis in lung cancer.