MyoD1 suppresses cell migration and invasion by inhibiting FUT4 transcription in human gastric cancer cells.

Myogenic differentiation 1 (MyoD1) is a transcription factor that promotes expression of muscle-specific genes. MyoD1 is expressed at significantly lower levels in gastric cancer (GC) tissues and cells, and it induces apoptosis in GC cells. However, functions for MyoD1 in GC cell migration and gene expression have not been documented. We show that knockdown of MyoD1 promoted migration and invasion of GC cells, whereas MyoD1 overexpression suppressed migration and invasion. We performed chromatin immunoprecipitation (ChIP)-sequencing to identify MyoD1 target genes in MKN-45 cells. The 2-kb upstream regions (Up2k) of the transcription start sites of 57 genes were probably bound by MyoD1. Six of these genes function in signaling pathways such as synthesis of glycosphingolipid biosynthesis-lacto and neolacto series. MyoD1 inhibited transcription of fucosyltransferase IV (FUT4) by binding directly to the FUT4 F3; this finding was validated by ChIP-quantitative PCR and a luciferase reporter assay. Ulex europaeus agglutinin I, which binds Fucα1-2Galβ1-4GlcNAc, and Lewis antigens showed decreased binding to the plasma membrane of cells that overexpressed MyoD1. Knockdown of FUT4 mimicked MyoD1 overexpression by suppressing GC cell migration and invasion; this result implied that MyoD1 suppressed cell migration and invasion via inhibiting the FUT4/matrix metallopeptidase signaling pathway. In summary, this study demonstrated that MyoD1 suppresses migration and invasion of GC cells by directly binding to the F3 region in the FUT4 Up2k and inhibiting FUT4/type II Lewis antigen expression.