Suppressor Of Cancer Cell Invasion (SCAI)

SCAI, a novel and highly conserved protein that regulates invasive cell migration through three-dimensional matrices. SCAI acts on the RhoA–Dia1 signal transduction pathway and localizes in the nucleus, where it binds and inhibits the myocardin-related transcription factor MAL by forming a ternary complex with serum response factor (SRF). Genome-wide expression analysis surprisingly reveals that one of the strongest upregulated genes after suppression of SCAI is b1-integrin. Decreased levels of SCAI are tightly correlated with increased invasive cell migration, and SCAI is downregulated in several human tumours. Functional analysis of the b1-integrin gene strongly argues that SCAI is a novel transcriptional cofactor that controls gene expression downstream of Dia1 to dictate changes in cell invasive behaviour.