| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Klinikum rechts der Isar,* Institut für Pathologie, Technische Universität München, München, Germany; Klinikum rechts der Isar, Institut für Medizinische Statistik und Epidemiologie, Technische Universität München, Muenchen, Germany; and Institut für Pathologie, GSF-Forschungszentrum für Umwelt und Gesundheit, Neuherberg, Germany
Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is thought to play a fundamental role during early steps of invasion and metastasis of carcinoma cells. The aim of our study was to elucidate the role of EMT regulators Snail, SIP1 (both are direct repressors of E-cadherin), and Twist (an activator of N-cadherin during Drosophila embryogenesis), in primary human gastric cancers. Expression of Snail, SIP1, and Twist was analyzed in 48 gastric carcinomas by real-time quantitative RT-PCR in paraffin-embedded and formalin-fixed tissues. The changes of expression levels of these genes in malignant tissues compared to matched non-tumorous tissues were correlated with the expression of E- and N-cadherin. From 28 diffuse-type gastric carcinomas analyzed reduced E-cadherin expression was detected in 11 (39%) cases compared to non-tumorous tissues. Up-regulated Snail could be found in 6 cases with reduced or negative E-cadherin expression. However, there was no correlation to increased SIP1 expression. Interestingly, we could detect abnormal expression of N-cadherin mRNA in 6 cases, which was correlated with Twist overexpression in 4 cases. From 20 intestinal-type gastric cancer samples reduced E-cadherin expression was found in 12 (60%) cases, which was correlated to up-regulation of SIP1, since 10 of these 12 cases showed elevated mRNA levels, whereas Snail, Twist, and N-cadherin were not up-regulated. We present the first study investigating the role of EMT regulators in human gastric cancer and provide evidence that an increase in Snail mRNA expression is associated with down-regulation of E-cadherin in diffuse-type gastric cancer. We detected abnormally positive or increased N-cadherin mRNA levels in the same tumors, probably due to overexpression of Twist. SIP1 overexpression could not be linked to down-regulated E-cadherin in diffuse-type tumors, but was found to be involved in the pathogenesis of intestinal-type gastric carcinoma. We conclude that EMT regulators play different roles in gastric carcinogenesis depending on the histological subtype.
This article has been cited by other articles:
 |
|
 |
|
  J. Heuberger and W. Birchmeier Interplay of Cadherin-Mediated Cell Adhesion and Canonical Wnt Signaling Cold Spring Harb Perspect Biol, February 1, 2010; 2(2): a002915 - a002915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Berx and F. van Roy Involvement of Members of the Cadherin Superfamily in Cancer Cold Spring Harb Perspect Biol, December 1, 2009; 1(6): a003129 - a003129. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bauer, A. Dowejko, A.-K. Bosserhoff, T.E. Reichert, and R. Josef Bauer P-cadherin induces an epithelial-like phenotype in oral squamous cell carcinoma by GSK-3beta-mediated Snail phosphorylation Carcinogenesis, October 1, 2009; 30(10): 1781 - 1788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. MIURA, T. YANO, F. SHOJI, D. KAWANO, T. TAKENAKA, K. ITO, Y. MORODOMI, I. YOSHINO, and Y. MAEHARA Clinicopathological Significance of Sip1-associated Epithelial Mesenchymal Transition in Non-small Cell Lung Cancer Progression Anticancer Res, October 1, 2009; 29(10): 4099 - 4106. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Sayan, T. R. Griffiths, R. Pal, G. J. Browne, A. Ruddick, T. Yagci, R. Edwards, N. J. Mayer, H. Qazi, S. Goyal, et al. SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer PNAS, September 1, 2009; 106(35): 14884 - 14889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-Y. Huang, Z.-G. Li, H. Rus, X. Wang, P. A. Jose, and S.-Y. Chen RGC-32 Mediates Transforming Growth Factor-{beta}-induced Epithelial-Mesenchymal Transition in Human Renal Proximal Tubular Cells J. Biol. Chem., April 3, 2009; 284(14): 9426 - 9432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. P. Bracken, P. A. Gregory, N. Kolesnikoff, A. G. Bert, J. Wang, M. F. Shannon, and G. J. Goodall A Double-Negative Feedback Loop between ZEB1-SIP1 and the microRNA-200 Family Regulates Epithelial-Mesenchymal Transition Cancer Res., October 1, 2008; 68(19): 7846 - 7854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Alix-Panabieres, S. Riethdorf, and K. Pantel Circulating Tumor Cells and Bone Marrow Micrometastasis Clin. Cancer Res., August 15, 2008; 14(16): 5013 - 5021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Hu, J. M. Roth, P. Brooks, S. Ibrahim, and S. Karpatkin Twist Is Required for Thrombin-Induced Tumor Angiogenesis and Growth Cancer Res., June 1, 2008; 68(11): 4296 - 4302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-M. Park, A. B. Gaur, E. Lengyel, and M. E. Peter The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2 Genes & Dev., April 1, 2008; 22(7): 894 - 907. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Wheelock, Y. Shintani, M. Maeda, Y. Fukumoto, and K. R. Johnson Cadherin switching J. Cell Sci., March 15, 2008; 121(6): 727 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Sun, M. E. Diamond, A. J. Ottaviano, M. J. Joseph, V. Ananthanarayan, and H. G. Munshi Transforming Growth Factor-{beta}1 Promotes Matrix Metalloproteinase-9-Mediated Oral Cancer Invasion through Snail Expression Mol. Cancer Res., January 1, 2008; 6(1): 10 - 20. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Mejlvang, M. Kriajevska, C. Vandewalle, T. Chernova, A. E. Sayan, G. Berx, J. K. Mellon, and E. Tulchinsky Direct Repression of Cyclin D1 by SIP1 Attenuates Cell Cycle Progression in Cells Undergoing an Epithelial Mesenchymal Transition Mol. Biol. Cell, November 1, 2007; 18(11): 4615 - 4624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Hardy, C. Vicente-Duenas, I. Gonzalez-Herrero, C. Anderson, T. Flores, S. Hughes, C. Tselepis, J. A. Ross, and I. Sanchez-Garcia Snail Family Transcription Factors Are Implicated in Thyroid Carcinogenesis Am. J. Pathol., September 1, 2007; 171(3): 1037 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zhang, Z. Jia, X. Guo, and T. Yang Aldosterone induces epithelial-mesenchymal transition via ROS of mitochondrial origin Am J Physiol Renal Physiol, September 1, 2007; 293(3): F723 - F731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Hotz, M. Arndt, S. Dullat, S. Bhargava, H.-J. Buhr, and H. G. Hotz Epithelial to Mesenchymal Transition: Expression of the Regulators Snail, Slug, and Twist in Pancreatic Cancer Clin. Cancer Res., August 15, 2007; 13(16): 4769 - 4776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. R. Christoffersen, A. Silahtaroglu, U. A. Orom, S. Kauppinen, and A. H. Lund miR-200b mediates post-transcriptional repression of ZFHX1B RNA, August 1, 2007; 13(8): 1172 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Mani, J. Yang, M. Brooks, G. Schwaninger, A. Zhou, N. Miura, J. L. Kutok, K. Hartwell, A. L. Richardson, and R. A. Weinberg Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers PNAS, June 12, 2007; 104(24): 10069 - 10074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. G. Pham, C. Bubici, F. Zazzeroni, J. R. Knabb, S. Papa, C. Kuntzen, and G. Franzoso Upregulation of Twist-1 by NF-{kappa}B Blocks Cytotoxicity Induced by Chemotherapeutic Drugs Mol. Cell. Biol., June 1, 2007; 27(11): 3920 - 3935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-J. Kim, B. C. Litzenburger, X. Cui, D. A. Delgado, B. C. Grabiner, X. Lin, M. T. Lewis, M. M. Gottardis, T. W. Wong, R. M. Attar, et al. Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and Is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-{kappa}B and Snail Mol. Cell. Biol., April 15, 2007; 27(8): 3165 - 3175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Larriba, N. Valle, H. G Palmer, P. Ordonez-Moran, S. Alvarez-Diaz, K.-F. Becker, C. Gamallo, A. G. de Herreros, J. M. Gonzalez-Sancho, and A. Munoz The inhibition of Wnt/{beta}-catenin signalling by 1{alpha},25-dihydroxyvitamin D3 is abrogated by Snail1 in human colon cancer cells Endocr. Relat. Cancer, March 1, 2007; 14(1): 141 - 151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Z. Cheng, J. Chan, Q. Wang, W. Zhang, C. D. Sun, and L.-H. Wang Twist Transcriptionally Up-regulates AKT2 in Breast Cancer Cells Leading to Increased Migration, Invasion, and Resistance to Paclitaxel Cancer Res., March 1, 2007; 67(5): 1979 - 1987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hayashida, Y. Urata, E. Muroi, T. Kono, Y. Miyata, K. Nomata, H. Kanetake, T. Kondo, and Y. Ihara Calreticulin Represses E-cadherin Gene Expression in Madin-Darby Canine Kidney Cells via Slug J. Biol. Chem., October 27, 2006; 281(43): 32469 - 32484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R.E. Rees, B. A. Onwuegbusi, V. E. Save, D. Alderson, and R. C. Fitzgerald In vivo and In vitro Evidence for Transforming Growth Factor-{beta}1-Mediated Epithelial to Mesenchymal Transition in Esophageal Adenocarcinoma Cancer Res., October 1, 2006; 66(19): 9583 - 9590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Lee, R. T.P. Poon, A. P. Yuen, M. T. Ling, W. K. Kwok, X. H. Wang, Y. C. Wong, X. Y. Guan, K. Man, K. L. Chau, et al. Twist Overexpression Correlates with Hepatocellular Carcinoma Metastasis through Induction of Epithelial-Mesenchymal Transition. Clin. Cancer Res., September 15, 2006; 12(18): 5369 - 5376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Come, F. Magnino, F. Bibeau, P. De Santa Barbara, K. F. Becker, C. Theillet, and P. Savagner Snail and Slug Play Distinct Roles during Breast Carcinoma Progression. Clin. Cancer Res., September 15, 2006; 12(18): 5395 - 5402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Vernon and C. LaBonne Slug stability is dynamically regulated during neural crest development by the F-box protein Ppa Development, September 1, 2006; 133(17): 3359 - 3370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. E. Turner, S. Broad, F. L. Khanim, A. Jeanes, S. Talma, S. Hughes, C. Tselepis, and N. A. Hotchin Slug Regulates Integrin Expression and Cell Proliferation in Human Epidermal Keratinocytes J. Biol. Chem., July 28, 2006; 281(30): 21321 - 21331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yang, S. A. Mani, and R. A. Weinberg Exploring a New Twist on Tumor Metastasis. Cancer Res., May 1, 2006; 66(9): 4549 - 4552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Lascombe, A. Clairotte, S. Fauconnet, S. Bernardini, H. Wallerand, B. Kantelip, and H. Bittard N-cadherin as a novel prognostic marker of progression in superficial urothelial tumors. Clin. Cancer Res., May 1, 2006; 12(9): 2780 - 2787. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Koster, S.-L. Lu, L. D. White, X.-J. Wang, and D. R. Roop Reactivation of Developmentally Expressed p63 Isoforms Predisposes to Tumor Development and Progression. Cancer Res., April 15, 2006; 66(8): 3981 - 3986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Alexander, N. L. Tran, H. Rekapally, C. E. Summers, C. Glackin, and R. L. Heimark N-cadherin Gene Expression in Prostate Carcinoma Is Modulated by Integrin-Dependent Nuclear Translocation of Twist1. Cancer Res., April 1, 2006; 66(7): 3365 - 3369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rosano, F. Spinella, V. Di Castro, M. R. Nicotra, S. Dedhar, A. G. de Herreros, P. G. Natali, and A. Bagnato Endothelin-1 Promotes Epithelial-to-Mesenchymal Transition in Human Ovarian Cancer Cells Cancer Res., December 15, 2005; 65(24): 11649 - 11657. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mironchik, P. T. Winnard Jr., F. Vesuna, Y. Kato, F. Wildes, A. P. Pathak, S. Kominsky, D. Artemov, Z. Bhujwalla, P. Van Diest, et al. Twist Overexpression Induces In vivo Angiogenesis and Correlates with Chromosomal Instability in Breast Cancer Cancer Res., December 1, 2005; 65(23): 10801 - 10809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Vandewalle, J. Comijn, B. De Craene, P. Vermassen, E. Bruyneel, H. Andersen, E. Tulchinsky, F. Van Roy, and G. Berx SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions Nucleic Acids Res., November 24, 2005; 33(20): 6566 - 6578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Pena, J. M. Garcia, J. Silva, V. Garcia, R. Rodriguez, I. Alonso, I. Millan, C. Salas, A. G. de Herreros, A. Munoz, et al. E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations Hum. Mol. Genet., November 15, 2005; 14(22): 3361 - 3370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Perez-Mancera, M. Perez-Caro, I. Gonzalez-Herrero, T. Flores, A. Orfao, A. G. de Herreros, A. Gutierrez-Adan, B. Pintado, A. Sagrera, M. Sanchez-Martin, et al. Cancer development induced by graded expression of Snail in mice Hum. Mol. Genet., November 15, 2005; 14(22): 3449 - 3461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tarin, E. W. Thompson, and D. F. Newgreen The Fallacy of Epithelial Mesenchymal Transition in Neoplasia Cancer Res., July 15, 2005; 65(14): 5996 - 6001. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. K. Kwok, M.-T. Ling, T.-W. Lee, T. C.M. Lau, C. Zhou, X. Zhang, C. W. Chua, K. W. Chan, F. L. Chan, C. Glackin, et al. Up-Regulation of TWIST in Prostate Cancer and Its Implication as a Therapeutic Target Cancer Res., June 15, 2005; 65(12): 5153 - 5162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Malta-Vacas, C Aires, P Costa, A R Conde, S Ramos, A P Martins, C Monteiro, and M Brito Differential expression of the eukaryotic release factor 3 (eRF3/GSPT1) according to gastric cancer histological types J. Clin. Pathol., June 1, 2005; 58(6): 621 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Napieralski, K. Ott, M. Kremer, K. Specht, H. Vogelsang, K. Becker, M. Muller, F. Lordick, U. Fink, J. Rudiger Siewert, et al. Combined GADD45A and Thymidine Phosphorylase Expression Levels Predict Response and Survival of Neoadjuvant-Treated Gastric Cancer Patients Clin. Cancer Res., April 15, 2005; 11(8): 3025 - 3031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Light, A. E. Vernon, A. Lasorella, A. Iavarone, and C. LaBonne Xenopus Id3 is required downstream of Myc for the formation of multipotent neural crest progenitor cells Development, April 15, 2005; 132(8): 1831 - 1841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Elliott and G. C. Blobe Role of Transforming Growth Factor Beta in Human Cancer J. Clin. Oncol., March 20, 2005; 23(9): 2078 - 2093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Maeda, K. R. Johnson, and M. J. Wheelock Cadherin switching: essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition J. Cell Sci., March 1, 2005; 118(5): 873 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Roy, P. Iversen, J. Hart, Y. Liu, J. L. Koetsier, Y. Kim, D. P. Kunte, M. Madugula, V. Backman, and R. K. Wali Down-regulation of SNAIL suppresses MIN mouse tumorigenesis: Modulation of apoptosis, proliferation, and fractal dimension Mol. Cancer Ther., September 1, 2004; 3(9): 1159 - 1165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vega, A. V. Morales, O. H. Ocana, F. Valdes, I. Fabregat, and M. A. Nieto Snail blocks the cell cycle and confers resistance to cell death Genes & Dev., May 15, 2004; 18(10): 1131 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Blindt, A.-K. Bosserhoff, J. Dammers, N. Krott, L. Demircan, R. Hoffmann, P. Hanrath, C. Weber, and F. Vogt Downregulation of N-cadherin in the neointima stimulates migration of smooth muscle cells by RhoA deactivation Cardiovasc Res, April 1, 2004; 62(1): 212 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Graziano, B. Humar, and P. Guilford The role of the E-cadherin gene (CDH1) in diffuse gastric cancer susceptibility: from the laboratory to clinical practice Ann. Onc., December 1, 2003; 14(12): 1705 - 1713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dominguez, B. Montserrat-Sentis, A. Virgos-Soler, S. Guaita, J. Grueso, M. Porta, I. Puig, J. Baulida, C. Franci, and A. Garcia de Herreros Phosphorylation Regulates the Subcellular Location and Activity of the Snail Transcriptional Repressor Mol. Cell. Biol., July 15, 2003; 23(14): 5078 - 5089. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. van Grunsven, C. Michiels, T. Van de Putte, L. Nelles, G. Wuytens, K. Verschueren, and D. Huylebroeck Interaction between Smad-interacting Protein-1 and the Corepressor C-terminal Binding Protein Is Dispensable for Transcriptional Repression of E-cadherin J. Biol. Chem., July 3, 2003; 278(28): 26135 - 26145. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
