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

被引：117

作者：

Brandt, Dominique T. ^{[1
]}

Baarlink, Christian ^{[1
]}

Kitzing, Thomas M. ^{[1
]}

Kremmer, Elisabeth ^{[2
]}

Ivaska, Johanna ^{[3
,4
]}

Nollau, Peter ^{[5
]}

Grosse, Robert ^{[1
]}

机构：

[1] Univ Heidelberg, Inst Pharmacol, D-69120 Heidelberg, Germany

[2] Helmholtz Zentrum Munchen, Inst Mol Immunol, D-81377 Munich, Germany

[3] VTT Tech Res Ctr Finland, FIN-20520 Turku, Finland

[4] Univ Turku, FIN-20520 Turku, Finland

[5] Univ Med Ctr Hamburg Eppendorf, Ctr Clin Pathol, Dept Clin Chem, D-20246 Hamburg, Germany

来源：

NATURE CELL BIOLOGY | 2009年 / 11卷 / 05期

基金：

欧洲研究理事会; 芬兰科学院;

关键词：

BREAST-CANCER; SRF ACTIVITY; MIGRATION; INTEGRIN; DYNAMICS; DIA1; BETA-1-INTEGRIN; COACTIVATOR; METASTASIS; MECHANISMS;

D O I：

10.1038/ncb1862

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：557 / U83

页数：19

共 32 条

[1] β1 integrin function in vivo:: Adhesion, migration and more [J].

Brakebusch, C ;

Fässler, R .

CANCER AND METASTASIS REVIEWS, 2005, 24 (03) :403-411

[2] Integrins in invasive growth [J].

Brakebusch, C ;

Bouvard, D ;

Stanchi, F ;

Saki, T ;

Fässler, R .

JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (08) :999-1006

[3] Dia1 and IQGAP1 interact in cell migration and phagocytic cup formation [J].

Brandt, Dominique T. ;

Marion, Sabrina ;

Griffiths, Gareth ;

Watanabe, Takashi ;

Kaibuchi, Kozo ;

Grosse, Robert .

JOURNAL OF CELL BIOLOGY, 2007, 178 (02) :193-200

[4] Mitf regulation of Dia1 controls melanoma proliferation and invasiveness [J].

Carreira, Suzanne ;

Goodall, Jane ;

Denat, Laurence ;

Rodriguez, Mercedes ;

Nuciforo, Paolo ;

Hoek, Keith S. ;

Testori, Alessandro ;

Larue, Lionel ;

Goding, Colin R. .

GENES & DEVELOPMENT, 2006, 20 (24) :3426-3439

[5] Rab25 associates with α5β1 integrin to promote invasive migration in 3D microenvironments [J].

Caswell, Patrick T. ;

Spence, Heather J. ;

Parsons, Maddy ;

White, Dominic P. ;

Clark, Katherine ;

Cheng, Kwai Wa ;

Mills, Gordon B. ;

Humphries, Martin J. ;

Messent, Anthea J. ;

Anderson, Kurt I. ;

McCaffrey, Mary W. ;

Ozanne, Bradford W. ;

Norman, Jim C. .

DEVELOPMENTAL CELL, 2007, 13 (04) :496-510

[6] Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes [J].

Cen, B ;

Selvaraj, A ;

Burgess, RC ;

Hitzler, JK ;

Ma, ZG ;

Morris, SW ;

Prywes, R .

MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (18) :6597-6608

[7] The diaphanous-related formin mDia1 controls serum response factor activity through its effects on actin polymerization [J].

Copeland, JW ;

Treisman, R .

MOLECULAR BIOLOGY OF THE CELL, 2002, 13 (11) :4088-4099

[8] Integrin signaling to the actin cytoskeleton [J].

DeMali, KA ;

Wennerberg, K ;

Burridge, K .

CURRENT OPINION IN CELL BIOLOGY, 2003, 15 (05) :572-582

[9] Staying in shape with formins [J].

Faix, Jan ;

Grosse, Robert .

DEVELOPMENTAL CELL, 2006, 10 (06) :693-706

[10] Functional interactions between the Forkhead transcription factor FOXK1 and the MADS-box protein SRF [J].

Freddie, Cecilie T. ;

Ji, Zongling ;

Marais, Anett ;

Sharrocks, Andrew D. .

NUCLEIC ACIDS RESEARCH, 2007, 35 (15) :5203-5212

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