SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of β1-integrin
Copyright policy )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). Genome-wide expression analysis surprisingly reveals that one of the strongest upregulated genes after suppression of SCAI is beta1-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 beta1-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.
- Universität Hamburg Germany
- Heidelberg University Germany
- University Medical Center Hamburg-Eppendorf Germany
- Finland University Finland
- Helmholtz Zentrum München Germany
Cell Nucleus, Binding Sites, Oncogene Proteins, Fusion, Integrin beta1, Molecular Sequence Data, Animal Structures, Down-Regulation, Gene Expression, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Mice, Enhancer Elements, Genetic, SDG 3 - Good Health and Well-being, Cell Movement, Cell Line, Tumor, Animals, Humans, Neoplasm Invasiveness, Amino Acid Sequence, Protein Binding
Cell Nucleus, Binding Sites, Oncogene Proteins, Fusion, Integrin beta1, Molecular Sequence Data, Animal Structures, Down-Regulation, Gene Expression, Cell Line, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Mice, Enhancer Elements, Genetic, SDG 3 - Good Health and Well-being, Cell Movement, Cell Line, Tumor, Animals, Humans, Neoplasm Invasiveness, Amino Acid Sequence, Protein Binding
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