SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of β₁-integrin

Gene expression reprogramming governs cellular processes such as proliferation, differentiation and cell migration through the complex and tightly regulated control of transcriptional cofactors that exist in multiprotein complexes. Here we describe SCAI (suppressor of cancer cell invasion), 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). Genomewide expression analysis surprisingly reveals that one of the strongest upregulated genes after suppression of SCAI is beta(1)-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 beta(1)-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

β-Catenin and Smad3 regulate the activity and stability of myocardin-related transcription factor during epithelial–myofibroblast transition

Two novel mechanisms are shown by which injury of intercellular junctions via β-catenin promotes epithelial–myofibroblast transition. β-Catenin interacts with Smad3, thereby preventing the inhibitory effect of the latter on myocardin-related transcription factor (MRTF), and maintains MRTF stability by inhibiting Smad3-mediated, GSK-3β–dependent degradation of MRTF