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

D. T. Brandt, C. Baarlink, T. M. Kitzing, E. Kremmer, Johanna Ivaska, P. Nollau, R. Grosse (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

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 β1-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 β1-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.
Original languageEnglish
Pages (from-to)557-568
JournalNature Cell Biology
Volume11
DOIs
Publication statusPublished - 2009
MoE publication typeA1 Journal article-refereed

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Integrins
Neoplasms
Cell Movement
Serum Response Factor
Gene Expression
Multiprotein Complexes
Genes
Signal Transduction
Transcription Factors
Down-Regulation
Genome
Proteins

Cite this

Brandt, D. T., Baarlink, C., Kitzing, T. M., Kremmer, E., Ivaska, J., Nollau, P., & Grosse, R. (2009). SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of β1-integrin. Nature Cell Biology, 11, 557-568. https://doi.org/10.1038/ncb1862
Brandt, D. T. ; Baarlink, C. ; Kitzing, T. M. ; Kremmer, E. ; Ivaska, Johanna ; Nollau, P. ; Grosse, R. / SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of β1-integrin. In: Nature Cell Biology. 2009 ; Vol. 11. pp. 557-568.
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Brandt, DT, Baarlink, C, Kitzing, TM, Kremmer, E, Ivaska, J, Nollau, P & Grosse, R 2009, 'SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of β1-integrin', Nature Cell Biology, vol. 11, pp. 557-568. https://doi.org/10.1038/ncb1862

SCAI acts as a suppressor of cancer cell invasion through the transcriptional control of β1-integrin. / Brandt, D. T.; Baarlink, C.; Kitzing, T. M.; Kremmer, E.; Ivaska, Johanna; Nollau, P.; Grosse, R. (Corresponding Author).

In: Nature Cell Biology, Vol. 11, 2009, p. 557-568.

Research output: Contribution to journalArticleScientificpeer-review

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