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Open Access Green as soon as Postprint is submitted to ZB.
SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of β₁-integrin.
Nat. Cell Biol. 11, 557-568 (2009)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
breast-cancer; srf activity; migration; integrin; dynamics; dia1; beta-1-integrin; coactivator; metastasis; mechanisms
ISSN (print) / ISBN
1465-7392
e-ISSN
1476-4679
Journal
Nature Cell Biology
Quellenangaben
Volume: 11,
Issue: 5,
Pages: 557-568
Publisher
Nature Publishing Group
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)