SUMMARY Epithelial-mesenchymal transition (EMT) enhances invasiveness and confers tumor cells with cancer stem cell (CSC)-like characteristics. We showed that the Snail-G9a-Dnmt1 complex, which is critical for E-cadherin promoter silencing, is also required for the promoter methylation of fructose-1,6-biphosphatase (FBP1) in basal-like breast cancer (BLBC). Loss of FBP1 induces glycolysis and results in increased glucose uptake, macromolecules biosynthesis, formation of tetrameric PKM2, and maintenance of ATP production under hypoxia. Loss of FBP1 also inhibits oxygen consumption and ROS production by suppressing mitochondrial complex I activity; this metabolic reprogramming results in an increased CSC-like property and tumorigenicity by enhancing the interaction of β-catenin with TCF. Our study indicates that the loss of FBP1 is a critical oncogenic event in EMT and BLBC.

Epithelial-mesenchymal transition (EMT) is a highly conserved process in which polarized, immotile epithelial cells lose adherent and tight junctions, and become migratory mesenchymal cells. As a key transcriptional repressor of E-cadherin expression in EMT, Snail plays an important role in embryonic development and cancer progression. Emerging evidences indicate that Snail confers tumor cells with cancer stem cell-like traits, and promotes drug resistance, tumor recurrence and metastasis. In this review, we summarize recent developments underlying the regulation and functions of Snail in tumor progression, and discuss new approaches against EMT in preventing metastatic cancers.

Summary Twist is a key transcription activator of epithelial-mesenchymal transition (EMT). It remains unclear how Twist induces gene expression. Here we reported a mechanism by which Twist recruits BRD4 to direct WNT5A expression in basal-like breast cancer (BLBC). Twist contains a “histone H4 mimic” GK-X-GK motif that is di-acetylated by Tip60. The di-acetylated Twist binds the second bromodomain of BRD4, whose first bromodomain interacts with acetylated H4, thereby constructs an activated Twist/BRD4/P-TEFb/RNA-PolII complex at the WNT5A promoter and enhancer. Pharmacologic inhibition of the Twist-BRD4 association reduced WNT5A expression and suppressed invasion, cancer stem cell (CSC)-like properties, and tumorigenicity of BLBC cells. Our study indicates that the interaction with BRD4 is critical for the oncogenic function of Twist in BLBC.