Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers

被引:202
作者
Alves, Catarina Castro [2 ]
Carneiro, Fatima [2 ]
Hoefler, Heinz [1 ,3 ]
Becker, Karl-Friedrich [1 ]
机构
[1] Tech Univ Munich, Inst Pathol, Trogerstr 18, D-81675 Munich, Germany
[2] Univ Porto, Inst Patol & Imunol Mol, P-4200465 Oporto, Portugal
[3] Deutsch Forschungszentrum Gesundheit & Umwelt GmB, Helmholtz Zentrum Muenchen, D-85764 Neuherberg, Germany
来源
FRONTIERS IN BIOSCIENCE-LANDMARK | 2009年 / 14卷
关键词
Cadherin; Adhesion; Transcription Factor; Invasion; Metastasis; Review; E-CADHERIN EXPRESSION; SQUAMOUS-CELL CARCINOMA; TRANSCRIPTION FACTORS SNAIL; REPRESSES E-CADHERIN; BREAST-CARCINOMA; HEPATOCELLULAR-CARCINOMA; TUMOR PROGRESSION; OVARIAN-CARCINOMA; MASTER REGULATOR; GENE-EXPRESSION;
D O I
10.2741/3433
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epithelial- mesenchymal- transition (EMT) is a crucial process during morphogenesis of multi-cellular organisms. EMT not only is a normal developmental process but also plays a role in tumor invasion and metastasis. Indeed, molecules involved in EMT, such as the transcription factor and E-cadherin repressor Slug (SNAI2), have recently been demonstrated to be important for cancer cells to down-regulate epithelial markers and up-regulate mesenchymal markers in order to become motile and invasive. Here we summarize major studies focusing on Slug expression in human tumor samples. We review a total of 13 studies involving 1150 cases from 9 different types of tumors. It is becoming clear that this transcription factor plays a role in the progression of some tumor types, including breast and gastric cancer. Interestingly, Slug expression is not always associated with down-regulation of E-cadherin. The mode of action, the signaling pathways involved in its regulation, and the interplay with other EMT regulators need to be addressed in future studies in order to fully understand Slug's role in tumor progression.
引用
收藏
页码:3041 / 3050
页数:10
相关论文
共 53 条
[11]   The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion [J].
Comijn, J ;
Berx, G ;
Vermassen, P ;
Verschueren, K ;
van Grunsven, L ;
Bruyneel, E ;
Mareel, M ;
Huylebroeck, D ;
van Roy, F .
MOLECULAR CELL, 2001, 7 (06) :1267-1278
[12]  
Davidson B, 2000, J PATHOL, V192, P460
[13]   Phosphorylation regulates the subcellular location and activity of the snail transcriptional repressor [J].
Domínguez, D ;
Montserrat-Sentís, B ;
Virgós-Soler, A ;
Guaita, S ;
Grueso, J ;
Porta, M ;
Puig, I ;
Baulida, J ;
Francí, C ;
de Herreros, AG .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (14) :5078-5089
[14]   Snail, slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma [J].
Elloul, S ;
Elstrand, MB ;
Nesland, JM ;
Tropé, CG ;
Kvalheim, G ;
Goldberg, I ;
Reich, R ;
Davidson, B .
CANCER, 2005, 103 (08) :1631-1643
[15]   Expression of E-cadherin transcriptional regulators in ovarian carcinoma [J].
Elloul, Sivan ;
Silins, Ilvars ;
Trope, Claes G. ;
Benshushan, Avi ;
Davidson, Ben ;
Reich, Reuven .
VIRCHOWS ARCHIV, 2006, 449 (05) :520-528
[16]   Hypermethylation-associated transcriptional silencing of E-cadherin in primary sporadic colorectal carcinomas [J].
Garinis, GA ;
Menounos, PG ;
Spanakis, NE ;
Papadopoulos, K ;
Karavitis, G ;
Parassi, I ;
Christeli, E ;
Patrinos, GP ;
Manolis, EN ;
Peros, G .
JOURNAL OF PATHOLOGY, 2002, 198 (04) :442-449
[17]   Immunohistological analysis of E-cadherin, α-, β- and γ-catenin expression in colorectal cancer:: Implications for cell adhesion and signaling [J].
Ghadimi, BM ;
Behrens, J ;
Hoffmann, I ;
Haensch, W ;
Birchmeier, W ;
Schlag, PM .
EUROPEAN JOURNAL OF CANCER, 1999, 35 (01) :60-65
[18]   Laminin-5 with transforming growth factor-β1 induces epithelial to mesenchymal transition in hepatocellular carcinoma [J].
Giannelli, G ;
Bergamini, C ;
Fransvea, E ;
Sgarra, C ;
Antonaci, S .
GASTROENTEROLOGY, 2005, 129 (05) :1375-1383
[19]   Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression [J].
Guaita, S ;
Puig, I ;
Francí, C ;
Garrido, M ;
Domínguez, D ;
Batlle, E ;
Sancho, E ;
Dedhar, S ;
de Herreros, AG ;
Baulida, J .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (42) :39209-39216
[20]   The melanocyte differentiation program predisposes to metastasis after neoplastic transformation [J].
Gupta, PB ;
Kuperwasser, C ;
Brunet, JP ;
Ramaswamy, S ;
Kuo, WL ;
Gray, JW ;
Naber, SP ;
Weinberg, RA .
NATURE GENETICS, 2005, 37 (10) :1047-1054