SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin.
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SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin. / Brandt, Dominique T; Baarlink, Christian; Kitzing, Thomas M; Kremmer, Elisabeth; Ivaska, Johanna; Nollau, Peter; Grosse, Robert.
In: NAT CELL BIOL, Vol. 11, No. 5, 5, 2009, p. 557-568.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of beta1-integrin.
AU - Brandt, Dominique T
AU - Baarlink, Christian
AU - Kitzing, Thomas M
AU - Kremmer, Elisabeth
AU - Ivaska, Johanna
AU - Nollau, Peter
AU - Grosse, Robert
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 11
SP - 557
EP - 568
JO - NAT CELL BIOL
JF - NAT CELL BIOL
SN - 1465-7392
IS - 5
M1 - 5
ER -
