Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Cancer and Metastasis Reviews
Erschienen in: Cancer and Metastasis Reviews 1-2/2009

01.06.2009

E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer

verfasst von: Otto Schmalhofer, Simone Brabletz, Thomas Brabletz

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 1-2/2009

Einloggen, um Zugang zu erhalten

Abstract

The embryonic program ‘epithelial-mesenchymal transition’ (EMT) is activated during tumor invasion in disseminating cancer cells. Characteristic to these cells is a loss of E-cadherin expression, which can be mediated by EMT-inducing transcriptional repressors, e.g. ZEB1. Consequences of a loss of E-cadherin are an impairment of cell-cell adhesion, which allows detachment of cells, and nuclear localization of β-catenin. In addition to an accumulation of cancer stem cells, nuclear β-catenin induces a gene expression pattern favoring tumor invasion, and mounting evidence indicates multiple reciprocal interactions of E-cadherin and β-catenin with EMT-inducing transcriptional repressors to stabilize an invasive mesenchymal phenotype of epithelial tumor cells.
Literatur
1.
Yilmaz, M., Christofori, G., & Lehembre, F. (2007). Distinct mechanisms of tumor invasion and metastasis. Trends in Molecular Medicine, 13, 535–541.PubMed
2.
Thiery, J. P. (2002). Epithelial-mesenchymal transitions in tumour progression. Nature Reviews Cancer, 2, 442–454.PubMed
3.
Takahashi, E., Funato, N., Higashihori, N., Hata, Y., Gridley, T., & Nakamura, M. (2004). Snail regulates p21(WAF/CIP1) expression in cooperation with E2A and Twist. Biochemical and Biophysical Research Communications, 325, 1136–1144.PubMed
4.
Yang, J., Mani, S. A., Donaher, J. L., Ramaswamy, S., Itzykson, R. A., Come, C., et al. (2004). Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell, 117, 927–939.PubMed
5.
Batlle, E., Sancho, E., Franci, C., Dominguez, D., Monfar, M., Baulida, J., et al. (2000). The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nature Cell Biology, 2, 84–89.PubMed
6.
Cano, A., Perez-Moreno, M. A., Rodrigo, I., Locascio, A., Blanco, M. J., del Barrio, M. G., et al. (2000). The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biology, 2, 76–83.PubMed
7.
Guaita, S., Puig, I., Franci, C., Garrido, M., Dominguez, D., Batlle, E., et al. (2002). Snail induction of epithelial to mesenchymal transition in tumor cells is accompanied by MUC1 repression and ZEB1 expression. Journal of Biological Chemistry, 277, 39209–39216.PubMed
8.
Peinado, H., Ballestar, E., Esteller, M., & Cano, A. (2004). Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Molecular and Cellular Biology, 24, 306–319.PubMed
9.
Hajra, K. M., Chen, D. Y., & Fearon, E. R. (2002). The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Research, 62, 1613–1618.PubMed
10.
Bolos, V., Peinado, H., Perez-Moreno, M. A., Fraga, M. F., Esteller, M., & Cano, A. (2003). The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. Journal of Cell Science, 116, 499–511.PubMed
11.
Comijn, J., Berx, G., Vermassen, P., Verschueren, K., van Grunsven, L., Bruyneel, E., et al. (2001). The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Molecular Cell, 7, 1267–1278.PubMed
12.
Grooteclaes, M. L., & Frisch, S. M. (2000). Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene, 19, 3823–3828.PubMed
13.
Funahashi, J., Sekido, R., Murai, K., Kamachi, Y., & Kondoh, H. (1993). Delta-crystallin enhancer binding protein delta EF1 is a zinc finger- homeodomain protein implicated in postgastrulation embryogenesis. Development, 119, 433–446.PubMed
14.
Eger, A., Aigner, K., Sonderegger, S., Dampier, B., Oehler, S., Schreiber, M., et al. (2005). DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene, 24, 2375–2385.PubMed
15.
Perez-Moreno, M., Jamora, C., & Fuchs, E. (2003). Sticky business: orchestrating cellular signals at adherens junctions. Cell, 112, 535–548.PubMed
16.
Perez-Moreno, M., & Fuchs, E. (2006). Catenins: keeping cells from getting their signals crossed. Developmental Cell, 11, 601–612.PubMed
17.
McNeill, H., Ozawa, M., Kemler, R., & Nelson, W. J. (1990). Novel function of the cell adhesion molecule uvomorulin as an inducer of cell surface polarity. Cell, 62, 309–316.PubMed
18.
Wheelock, M. J., & Johnson, K. R. (2003). Cadherins as modulators of cellular phenotype. Annual Review of Cell and Developmental Biology, 19, 207–235.PubMed
19.
Brabletz, T., Hlubek, F., Spaderna, S., Schmalhofer, O., Hiendlmeyer, E., Jung, A., et al. (2005). Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs, 179, 56–65.PubMed
20.
De Vries, W. N., Evsikov, A. V., Haac, B. E., Fancher, K. S., Holbrook, A. E., Kemler, R., et al. (2004). Maternal beta-catenin and E-cadherin in mouse development. Development, 131, 4435–4445.PubMed
21.
Nose, A., & Takeichi, M. (1986). A novel cadherin cell adhesion molecule: its expression patterns associated with implantation and organogenesis of mouse embryos. Journal of Cell Biology, 103, 2649–2658.PubMed
22.
Butz, S., & Larue, L. (1995). Expression of catenins during mouse embryonic development and in adult tissues. Cell Adhesion and Communication, 3, 337–352.PubMed
23.
Takeichi, M. (1988). The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development, 102, 639–655.PubMed
24.
Carver, E. A., Jiang, R., Lan, Y., Oram, K. F., & Gridley, T. (2001). The mouse snail gene encodes a key regulator of the epithelial-mesenchymal transition. Molecular and Cellular Biology, 21, 8184–8188.PubMed
25.
Huber, O., Bierkamp, C., & Kemler, R. (1996). Cadherins and catenins in development. Current Opinion in Cell Biology, 8, 685–691.PubMed
26.
Barbara, G., De Giorgio, R., Stanghellini, V., Corinaldesi, R., Cremon, C., Gerard, N., et al. (2003). Neutral endopeptidase (EC 3.4.24.11) downregulates the onset of intestinal inflammation in the nematode infected mouse. Gut, 52, 1457–1464.PubMed
27.
Matsunami, H., & Takeichi, M. (1995). Fetal brain subdivisions defined by R- and E-cadherin expressions: evidence for the role of cadherin activity in region-specific, cell-cell adhesion. Developmental Biology, 172, 466–478.PubMed
28.
Shimamura, K., Hirano, S., McMahon, A. P., & Takeichi, M. (1994). Wnt-1-dependent regulation of local E-cadherin and alpha N-catenin expression in the embryonic mouse brain. Development, 120, 2225–2234.PubMed
29.
Shimamura, K., & Takeichi, M. (1992). Local and transient expression of E-cadherin involved in mouse embryonic brain morphogenesis. Development, 116, 1011–1019.PubMed
30.
Shimamura, K., Takahashi, T., & Takeichi, M. (1992). E-cadherin expression in a particular subset of sensory neurons. Developmental Biology, 152, 242–254.PubMed
31.
Nishimura, E. K., Yoshida, H., Kunisada, T., & Nishikawa, S. I. (1999). Regulation of E- and P-cadherin expression correlated with melanocyte migration and diversification. Developmental Biology, 215, 155–166.PubMed
32.
Larue, L., Antos, C., Butz, S., Huber, O., Delmas, V., Dominis, M., et al. (1996). A role for cadherins in tissue formation. Development, 122, 3185–3194.PubMed
33.
Riethmacher, D., Brinkmann, V., & Birchmeier, C. (1995). A targeted mutation in the mouse E-cadherin gene results in defective preimplantation development. Proceedings of the National Academy of Sciences of the United States of America, 92, 855–859.PubMed
34.
Larue, L., Ohsugi, M., Hirchenhain, J., & Kemler, R. (1994). E-cadherin null mutant embryos fail to form a trophectoderm epithelium. Proceedings of the National Academy of Sciences of the United States of America, 91, 8263–8267.PubMed
35.
Boussadia, O., Kutsch, S., Hierholzer, A., Delmas, V., & Kemler, R. (2002). E-cadherin is a survival factor for the lactating mouse mammary gland. Mechanisms of Development, 115, 53–62.PubMed
36.
Tunggal, J. A., Helfrich, I., Schmitz, A., Schwarz, H., Gunzel, D., Fromm, M., et al. (2005). E-cadherin is essential for in vivo epidermal barrier function by regulating tight junctions. EMBO Journal, 24, 1146–1156.PubMed
37.
Cali, G., Zannini, M., Rubini, P., Tacchetti, C., D’Andrea, B., Affuso, A., et al. (2007). Conditional inactivation of the E-cadherin gene in thyroid follicular cells affects gland development but does not impair junction formation. Endocrinology, 148, 2737–2746.PubMed
38.
Tinkle, C. L., Lechler, T., Pasolli, H. A., & Fuchs, E. (2004). Conditional targeting of E-cadherin in skin: insights into hyperproliferative and degenerative responses. Proceedings of the National Academy of Sciences of the United States of America, 101, 552–557.PubMed
39.
Young, P., Boussadia, O., Halfter, H., Grose, R., Berger, P., Leone, D. P., et al. (2003). E-cadherin controls adherens junctions in the epidermis and the renewal of hair follicles. EMBO Journal, 22, 5723–5733.PubMed
40.
Hermiston, M. L., Wong, M. H., & Gordon, J. I. (1996). Forced expression of E-cadherin in the mouse intestinal epithelium slows cell migration and provides evidence for nonautonomous regulation of cell fate in a self-renewing system. Genes and Development, 10, 985–996.PubMed
41.
Cavallaro, U., & Christofori, G. (2004). Cell adhesion and signalling by cadherins and Ig-CAMs in cancer. Nature Reviews Cancer, 4, 118–132.PubMed
42.
Gottardi, C. J., Wong, E., & Gumbiner, B. M. (2001). E-cadherin suppresses cellular transformation by inhibiting beta-catenin signaling in an adhesion-independent manner. Journal of Cell Biology, 153, 1049–1060.PubMed
43.
Kuphal, F., & Behrens, J. (2006). E-cadherin modulates Wnt-dependent transcription in colorectal cancer cells but does not alter Wnt-independent gene expression in fibroblasts. Experimental Cell Research, 312, 457–467.PubMed
44.
Onder, T. T., Gupta, P. B., Mani, S. A., Yang, J., Lander, E. S., & Weinberg, R. A. (2008). Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Research, 68, 3645–3654.PubMed
45.
van Noort, M., & Clevers, H. (2002). TCF transcription factors, mediators of Wnt-signaling in development and cancer. Developmental Biology, 244, 1–8.PubMed
46.
Behrens, J., Jerchow, B. A., Wurtele, M., Grimm, J., Asbrand, C., Wirtz, R., et al. (1998). Functional interaction of an axin homolog, conductin, with beta- catenin, APC, and GSK3beta. Science, 280, 596–599.PubMed
47.
Kishida, S., Yamamoto, H., Ikeda, S., Kishida, M., Sakamoto, I., Koyama, S., et al. (1998). Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin. Journal of Biological Chemistry, 273, 10823–10826.PubMed
48.
Amit, S., Hatzubai, A., Birman, Y., Andersen, J. S., Ben-Shushan, E., Mann, M., et al. (2002). Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes and Development, 16, 1066–1076.PubMed
49.
Liu, C., Li, Y., Semenov, M., Han, C., Baeg, G. H., Tan, Y., et al. (2002). Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell, 108, 837–847.PubMed
50.
Kitagawa, M., Hatakeyama, S., Shirane, M., Matsumoto, M., Ishida, N., Hattori, K., et al. (1999). An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin. EMBO Journal, 18, 2401–2410.PubMed
51.
Fodde, R., Smits, R., & Clevers, H. (2001). APC, signal transduction and genetic instability in colorectal cancer. Nature Reviews Cancer, 1, 55–67.PubMed
52.
Wehrli, M., Dougan, S. T., Caldwell, K., O’Keefe, L., Schwartz, S., Vaizel-Ohayon, D., et al. (2000). Arrow encodes an LDL-receptor-related protein essential for Wingless signalling. Nature, 407, 527–530.PubMed
53.
Pinson, K. I., Brennan, J., Monkley, S., Avery, B. J., & Skarnes, W. C. (2000). An LDL-receptor-related protein mediates Wnt signalling in mice. Nature, 407, 535–538.PubMed
54.
Yanagawa, S., van Leeuwen, F., Wodarz, A., Klingensmith, J., & Nusse, R. (1995). The dishevelled protein is modified by wingless signaling in Drosophila. Genes and Development, 9, 1087–1097.PubMed
55.
Korinek, V., Barker, N., Morin, P. J., van Wichen, D., de Weger, R., Kinzler, K. W., et al. (1997). Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma [see comments]. Science, 275, 1784–1787.PubMed
56.
Behrens, J., von Kries, J. P., Kuhl, M., Bruhn, L., Wedlich, D., Grosschedl, R., et al. (1996). Functional interaction of beta-catenin with the transcription factor LEF-1. Nature, 382, 638–642.PubMed
57.
Clevers, H., & van de Wetering, M. (1997). TCF/LEF factor earn their wings. Trends in Genetics, 13, 485–489.PubMed
58.
Kramps, T., Peter, O., Brunner, E., Nellen, D., Froesch, B., Chatterjee, S., et al. (2002). Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell, 109, 47–60.PubMed
59.
Takemaru, K., Yamaguchi, S., Lee, Y. S., Zhang, Y., Carthew, R. W., & Moon, R. T. (2003). Chibby, a nuclear beta-catenin-associated antagonist of the Wnt/Wingless pathway. Nature, 422, 905–909.PubMed
60.
Takemaru, K. I., & Moon, R. T. (2000). The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. Journal of Cell Biology, 149, 249–254.PubMed
61.
Barker, N., Hurlstone, A., Musisi, H., Miles, A., Bienz, M., & Clevers, H. (2001). The chromatin remodelling factor Brg-1 interacts with beta-catenin to promote target gene activation. EMBO Journal, 20, 4935–4943.PubMed
62.
Pollheimer, J., Loregger, T., Sonderegger, S., Saleh, L., Bauer, S., Bilban, M., et al. (2006). Activation of the canonical wingless/t-cell factor signaling pathway promotes invasive differentiation of human trophoblast. American Journal of Pathology, 168, 1134–1147.PubMed
63.
Cadigan, K. M., & Nusse, R. (1997). Wnt signaling: a common theme in animal development. Genes and Development, 11, 3286–3305.PubMed
64.
Angerer, L., & Angerer, R. (1999). Regulative development of the sea urchin embryo: signalling cascades and morphogen gradients. Seminars in Cell and Developmental Biology, 10, 327–334.PubMed
65.
Liebner, S., Cattelino, A., Gallini, R., Rudini, N., Iurlaro, M., Piccolo, S., et al. (2004). Beta-catenin is required for endothelial-mesenchymal transformation during heart cushion development in the mouse. Journal of Cell Biology, 166, 359–367.PubMed
66.
Haegel, H., Larue, L., Ohsugi, M., Fedorov, L., Herrenknecht, K., & Kemler, R. (1995). Lack of beta-catenin affects mouse development at gastrulation. Development, 121, 3529–3537.PubMed
67.
Gat, U., DasGupta, R., Degenstein, L., & Fuchs, E. (1998). De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin. Cell, 95, 605–614.PubMed
68.
Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G., & Birchmeier, W. (2001). beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell, 105, 533–545.PubMed
69.
Staal, F. J., Meeldijk, J., Moerer, P., Jay, P., van de Weerdt, B. C., Vainio, S., et al. (2001). Wnt signaling is required for thymocyte development and activates Tcf-1 mediated transcription. European Journal of Immunology, 31, 285–293.PubMed
70.
Brault, V., Moore, R., Kutsch, S., Ishibashi, M., Rowitch, D. H., McMahon, A. P., et al. (2001). Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development, 128, 1253–1264.PubMed
71.
Ishikawa, T., Tamai, Y., Zorn, A. M., Yoshida, H., Seldin, M. F., Nishikawa, S., et al. (2001). Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Development, 128, 25–33.PubMed
72.
Ross, S. E., Hemati, N., Longo, K. A., Bennett, C. N., Lucas, P. C., Erickson, R. L., et al. (2000). Inhibition of adipogenesis by Wnt signaling. Science, 289, 950–953.PubMed
73.
Barker, N., Huls, G., Korinek, V., & Clevers, H. (1999). Restricted high level expression of Tcf-4 protein in intestinal and mammary gland epithelium. American Journal of Pathology, 154, 29–35.PubMed
74.
Korinek, V., Barker, N., Moerer, P., van Donselaar, E., Huls, G., Peters, P. J., et al. (1998). Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nature Genetics, 19, 379–383.PubMed
75.
Taipale, J., & Beachy, P. A. (2001). The Hedgehog and Wnt signalling pathways in cancer. Nature, 411, 349–354.PubMed
76.
Herzig, M., Savarese, F., Novatchkova, M., Semb, H., & Christofori, G. (2007). Tumor progression induced by the loss of E-cadherin independent of beta-catenin/Tcf-mediated Wnt signaling. Oncogene, 26, 2290–2298.PubMed
77.
van de Wetering, M., Barker, N., Harkes, I. C., van der Heyden, M., Dijk, N. J., Hollestelle, A., et al. (2001). Mutant E-cadherin breast cancer cells do not display constitutive Wnt signaling. Cancer Research, 61, 278–284.PubMed
78.
Rubinfeld, B., Souza, B., Albert, I., Muller, O., Chamberlain, S. H., Masiarz, F. R., et al. (1993). Association of the APC gene product with beta-catenin. Science, 262, 1731–1734.PubMed
79.
Huelsken, J., & Behrens, J. (2002). The Wnt signalling pathway. Jouranl of Cell Science, 115, 3977–3978.
80.
Perl, A. K., Wilgenbus, P., Dahl, U., Semb, H., & Christofori, G. (1998). A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature, 392, 190–193.PubMed
81.
Birchmeier, W., & Behrens, J. (1994). Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochimica et Biophysica Acta, 1198, 11–26.PubMed
82.
Behrens, J., Mareel, M. M., Van Roy, F. M., & Birchmeier, W. (1989). Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. Journal of Cell Biology, 108, 2435–2447.PubMed
83.
Frixen, U. H., Behrens, J., Sachs, M., Eberle, G., Voss, B., Warda, A., et al. (1991). E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. Journal of Cell Biology, 113, 173–185.PubMed
84.
Vleminckx, K., Vakaet Jr., L., Mareel, M., Fiers, W., & van Roy, F. (1991). Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell, 66, 107–119.PubMed
85.
Takeichi, M. (1995). Morphogenetic roles of classic cadherins. Current Opinion in Cell Biology, 7, 619–627.PubMed
86.
Kemler, R. (1993). From Cadherins to Catenins: cytoplasmic proetin interactions and regulation of cell adhesion. Trend in Genetics, 9, 317–321.
87.
Berx, G., Cleton-Jansen, A. M., Strumane, K., de Leeuw, W. J., Nollet, F., van Roy, F., et al. (1996). E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene, 13, 1919–1925.PubMed
88.
Risinger, J. I., Berchuck, A., Kohler, M. F., & Boyd, J. (1994). Mutations of the E-cadherin gene in human gynecologic cancers. Nature Genetics, 7, 98–102.PubMed
89.
Oda, T., Kanai, Y., Oyama, T., Yoshiura, K., Shimoyama, Y., Birchmeier, W., et al. (1994). E-cadherin gene mutations in human gastric carcinoma cell lines. Proceedings of the National Academy of Sciences of the United States of America, 91, 1858–1862.PubMed
90.
Tamura, G., Sakata, K., Nishizuka, S., Maesawa, C., Suzuki, Y., Iwaya, T., et al. (1996). Inactivation of the E-cadherin gene in primary gastric carcinomas and gastric carcinoma cell lines. Japanese Journal of Cancer Research, 87, 1153–1159.PubMed
91.
Guilford, P., Hopkins, J., Harraway, J., McLeod, M., McLeod, N., Harawira, P., et al. (1998). E-cadherin germline mutations in familial gastric cancer. Nature, 392, 402–405.PubMed
92.
Guilford, P. J., Hopkins, J. B., Grady, W. M., Markowitz, S. D., Willis, J., Lynch, H., et al. (1999). E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. Human Mutation, 14, 249–255.PubMed
93.
Graff, J. R., Gabrielson, E., Fujii, H., Baylin, S. B., & Herman, J. G. (2000). Methylation patterns of the E-cadherin 5′ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. Journal of Biological Chemistry, 275, 2727–2732.PubMed
94.
Lynch, H. T., Grady, W., Lynch, J. F., Tsuchiya, K. D., Wiesner, G., & Markowitz, S. D. (2000). E-cadherin mutation-based genetic counseling and hereditary diffuse gastric carcinoma. Cancer Genet Cytogenet, 122, 1–6.PubMed
95.
Caldeira, J. R., Prando, E. C., Quevedo, F. C., Neto, F. A., Rainho, C. A., & Rogatto, S. R. (2006). CDH1 promoter hypermethylation and E-cadherin protein expression in infiltrating breast cancer. BMC Cancer, 6, 48.PubMed
96.
Nass, S. J., Herman, J. G., Gabrielson, E., Iversen, P. W., Parl, F. F., Davidson, N. E., et al. (2000). Aberrant methylation of the estrogen receptor and E-cadherin 5′ CpG islands increases with malignant progression in human breast cancer. Cancer Research, 60, 4346–4348.PubMed
97.
Azarschab, P., Stembalska, A., Loncar, M. B., Pfister, M., Sasiadek, M. M., & Blin, N. (2003). Epigenetic control of E-cadherin (CDH1) by CpG methylation in metastasising laryngeal cancer. Oncology Reports, 10, 501–503.PubMed
98.
Wheeler, J. M., Kim, H. C., Efstathiou, J. A., Ilyas, M., Mortensen, N. J., & Bodmer, W. F. (2001). Hypermethylation of the promoter region of the E-cadherin gene (CDH1) in sporadic and ulcerative colitis associated colorectal cancer. Gut, 48, 367–371.PubMed
99.
Vicovac, L., & Aplin, J. D. (1996). Epithelial-mesenchymal transition during trophoblast differentiation. Acta Anat (Basel), 156, 202–216.
100.
Bloch-Zupan, A., Hunter, N., Manthey, A., & Gibbins, J. (2001). R-twist gene expression during rat palatogenesis. International Journal of Developmental Biology, 45, 397–404.PubMed
101.
Selleck, M. A., & Bronner-Fraser, M. (2000). Avian neural crest cell fate decisions: a diffusible signal mediates induction of neural crest by the ectoderm. International Journal of Developmental Neuroscience, 18, 621–627.PubMed
102.
Fata, J. E., Werb, Z., & Bissell, M. J. (2004). Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes. Breast Cancer Research, 6, 1–11.PubMed
103.
Viebahn, C. (1995). Epithelio-mesenchymal transformation during formation of the mesoderm in the mammalian embryo. Acta Anatomica, 154, 79–97.PubMed
104.
Kim, K., Lu, Z., & Hay, E. D. (2002). Direct evidence for a role of beta-catenin/LEF-1 signaling pathway in induction of EMT. Cell Biology International, 26, 463–476.PubMed
105.
Lee, J. M., Dedhar, S., Kalluri, R., & Thompson, E. W. (2006). The epithelial-mesenchymal transition: new insights in signaling, development, and disease. Journal of Cell Biology, 172, 973–981.PubMed
106.
Agiostratidou, G., Hulit, J., Phillips, G. R., & Hazan, R. B. (2007). Differential cadherin expression: potential markers for epithelial to mesenchymal transformation during tumor progression. Journal of Mammary Gland Biology and Neoplasia, 12, 127–133.PubMed
107.
Thiery, J. P., & Sleeman, J. P. (2006). Complex networks orchestrate epithelial-mesenchymal transitions. Nature Reviews Molecular Cell Biology, 7, 131–142.PubMed
108.
Morel, A. P., Lievre, M., Thomas, C., Hinkal, G., Ansieau, S., & Puisieux, A. (2008). Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS ONE, 3, e2888.PubMed
109.
Mani, S. A., Guo, W., Liao, M. J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., et al. (2008). The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133, 704–715.PubMed
110.
Peinado, H., Olmeda, D., & Cano, A. (2007). Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nature Reviews Cancer, 7, 415–428.PubMed
111.
Lai, Z. C., Fortini, M. E., & Rubin, G. M. (1991). The embryonic expression patterns of zfh-1 and zfh-2, two Drosophila genes encoding novel zinc-finger homeodomain proteins. Mechanisms of Development, 34, 123–134.PubMed
112.
Lai, Z. C., Rushton, E., Bate, M., & Rubin, G. M. (1993). Loss of function of the Drosophila zfh-1 gene results in abnormal development of mesodermally derived tissues. Proceedings of the National Academy of Sciences of the United States of America, 90, 4122–4126.PubMed
113.
Takagi, T., Moribe, H., Kondoh, H., & Higashi, Y. (1998). DeltaEF1, a zinc finger and homeodomain transcription factor, is required for skeleton patterning in multiple lineages. Development, 125, 21–31.PubMed
114.
Higashi, Y., Moribe, H., Takagi, T., Sekido, R., Kawakami, K., Kikutani, H., et al. (1997). Impairment of T cell development in deltaEF1 mutant mice. Journal of Experimental Medicine, 185, 1467–1479.PubMed
115.
Liu, Y., El-Naggar, S., Darling, D. S., Higashi, Y., & Dean, D. C. (2008). Zeb1 links epithelial-mesenchymal transition and cellular senescence. Development, 135, 579–588.PubMed
116.
Genetta, T., Ruezinsky, D., & Kadesch, T. (1994). Displacement of an E-box-binding repressor by basic helix-loop-helix proteins: implications for B-cell specificity of the immunoglobulin heavy-chain enhancer. Molecular and Cellular Biology, 14, 6153–6163.PubMed
117.
Williams, T. M., Moolten, D., Burlein, J., Romano, J., Bhaerman, R., Godillot, A., et al. (1991). Identification of a zinc finger protein that inhibits IL-2 gene expression. Science, 254, 1791–1794.PubMed
118.
Kraus, R. J., Perrigoue, J. G., & Mertz, J. E. (2003). ZEB negatively regulates the lytic-switch BZLF1 gene promoter of Epstein-Barr virus. Journal of Virology, 77, 199–207.PubMed
119.
Remacle, J. E., Kraft, H., Lerchner, W., Wuytens, G., Collart, C., Verschueren, K., et al. (1999). New mode of DNA binding of multi-zinc finger transcription factors: deltaEF1 family members bind with two hands to two target sites. EMBO Journal, 18, 5073–5084.PubMed
120.
Gregoire, J. M., & Romeo, P. H. (1999). T-cell expression of the human GATA-3 gene is regulated by a non- lineage-specific silencer. Journal of Biological Chemistry, 274, 6567–6578.PubMed
121.
Fontemaggi, G., Gurtner, A., Strano, S., Higashi, Y., Sacchi, A., Piaggio, G., et al. (2001). The transcriptional repressor ZEB regulates p73 expression at the crossroad between proliferation and differentiation. Molecular and Cellular Biology, 21, 8461–8470.PubMed
122.
Murray, D., Precht, P., Balakir, R., & Horton Jr., W. E. (2000). The transcription factor deltaEF1 is inversely expressed with type II collagen mRNA and can repress Col2a1 promoter activity in transfected chondrocytes. Journal of Biological Chemistry, 275, 3610–3618.PubMed
123.
Terraz, C., Toman, D., Delauche, M., Ronco, P., & Rossert, J. (2001). delta Ef1 binds to a far upstream sequence of the mouse pro-alpha 1(I) collagen gene and represses its expression in osteoblasts. Journal of Biological Chemistry, 276, 37011–37019.PubMed
124.
Brabletz, T., Jung, A., Hlubek, F., Lohberg, C., Meiler, J., Suchy, U., et al. (1999). Negative regulation of CD4 expression in T cells by the transcriptional repressor ZEB. International Immunology, 11, 1701–1708.PubMed
125.
Nishimura, G., Manabe, I., Tsushima, K., Fujiu, K., Oishi, Y., Imai, Y., et al. (2006). DeltaEF1 mediates TGF-beta signaling in vascular smooth muscle cell differentiation. Developmental Cell, 11, 93–104.PubMed
126.
Chamberlain, E. M., & Sanders, M. M. (1999). Identification of the novel player deltaEF1 in estrogen transcriptional cascades. Molecular Cellular Biology, 19, 3600–3606.
127.
Lazarova, D. L., Bordonaro, M., & Sartorelli, A. C. (2001). Transcriptional regulation of the vitamin D(3) receptor gene by ZEB. Cell Growth and Differentiation, 12, 319–326.PubMed
128.
Postigo, A. A. (2003). Opposing functions of ZEB proteins in the regulation of the TGFbeta/BMP signaling pathway. EMBO Journal, 22, 2443–2452.PubMed
129.
Postigo, A. A., Depp, J. L., Taylor, J. J., & Kroll, K. L. (2003). Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins. EMBO Journal, 22, 2453–2462.PubMed
130.
van Grunsven, L. A., Taelman, V., Michiels, C., Opdecamp, K., Huylebroeck, D., & Bellefroid, E. J. (2006). deltaEF1 and SIP1 are differentially expressed and have overlapping activities during Xenopus embryogenesis. Developmental Dynamics, 235, 1491–1500.PubMed
131.
Korpal, M., Lee, E. S., Hu, G., & Kang, Y. (2008). The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. Journal of Biological Chemistry, 283, 14910–14914.PubMed
132.
Gregory, P. A., Bert, A. G., Paterson, E. L., Barry, S. C., Tsykin, A., Farshid, G., et al. (2008). The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biology, 10, 593–601.PubMed
133.
Gilles, C., Polette, M., Birembaut, P., Brunner, N., & Thompson, E. W. (1997). Expression of c-ets-1 mRNA is associated with an invasive, EMT-derived phenotype in breast carcinoma cell lines. Clinical and Experimental Metastasis, 15, 519–526.PubMed
134.
Rodrigo, I., Cato, A. C., & Cano, A. (1999). Regulation of E-cadherin gene expression during tumor progression: the role of a new Ets-binding site and the E-pal element. Experimental Cell Research, 248, 358–371.PubMed
135.
Burk, U., Schubert, J., Wellner, U., Schmalhofer, O., Vincan, E., Spaderna, S., et al. (2008). A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Report, 9, 582–589.
136.
Chua, H. L., Bhat-Nakshatri, P., Clare, S. E., Morimiya, A., Badve, S., & Nakshatri, H. (2007). NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2. Oncogene, 26, 711–724.PubMed
137.
Irie, H. Y., Pearline, R. V., Grueneberg, D., Hsia, M., Ravichandran, P., Kothari, N., et al. (2005). Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition. Journal of Cell Biology, 171, 1023–1034.PubMed
138.
Kawada, M., Inoue, H., Masuda, T., & Ikeda, D. (2006). Insulin-like growth factor I secreted from prostate stromal cells mediates tumor-stromal cell interactions of prostate cancer. Cancer Research, 66, 4419–4425.PubMed
139.
Miyamoto, S., Nakamura, M., Shitara, K., Nakamura, K., Ohki, Y., Ishii, G., et al. (2005). Blockade of paracrine supply of insulin-like growth factors using neutralizing antibodies suppresses the liver metastasis of human colorectal cancers. Clinical Cancer Research, 11, 3494–3502.PubMed
140.
Graham, T. R., Zhau, H. E., Odero-Marah, V. A., Osunkoya, A. O., Kimbro, K. S., Tighiouart, M., et al. (2008). Insulin-like growth factor-I-dependent up-regulation of ZEB1 drives epithelial-to-mesenchymal transition in human prostate cancer cells. Cancer Research, 68, 2479–2488.PubMed
141.
Weber, K. L., Doucet, M., & Price, J. E. (2003). Renal cell carcinoma bone metastasis: epidermal growth factor receptor targeting. Clin Orthop Relat Res, 415, S86–94.
142.
Verbeek, B. S., Adriaansen-Slot, S. S., Vroom, T. M., Beckers, T., & Rijksen, G. (1998). Overexpression of EGFR and c-erbB2 causes enhanced cell migration in human breast cancer cells and NIH3T3 fibroblasts. FEBS Letters, 425, 145–150.PubMed
143.
Lu, Z., Ghosh, S., Wang, Z., & Hunter, T. (2003). Downregulation of caveolin-1 function by EGF leads to the loss of E-cadherin, increased transcriptional activity of beta-catenin, and enhanced tumor cell invasion. Cancer Cell, 4, 499–515.PubMed
144.
Wang, F., Sloss, C., Zhang, X., Lee, S. W., & Cusack, J. C. (2007). Membrane-bound heparin-binding epidermal growth factor like growth factor regulates E-cadherin expression in pancreatic carcinoma cells. Cancer Research, 67, 8486–8493.PubMed
145.
Yang, L., Amann, J. M., Kikuchi, T., Porta, R., Guix, M., Gonzalez, A., et al. (2007). Inhibition of epidermal growth factor receptor signaling elevates 15-hydroxyprostaglandin dehydrogenase in non-small-cell lung cancer. Cancer Research, 67, 5587–5593.PubMed
146.
Richer, J. K., Jacobsen, B. M., Manning, N. G., Abel, M. G., Wolf, D. M., & Horwitz, K. B. (2002). Differential gene regulation by the two progesterone receptor isoforms in human breast cancer cells. Journal of Biological Chemistry, 277, 5209–5218.PubMed
147.
Dohadwala, M., Yang, S. C., Luo, J., Sharma, S., Batra, R. K., Huang, M., et al. (2006). Cyclooxygenase-2-dependent regulation of E-Cadherin: prostaglandin E2 induces transcriptional repressors ZEB1 and snail in non-small cell lung cancer. Cancer Research, 66, 5338–5345.PubMed
148.
Manavella, P. A., Roqueiro, G., Darling, D. S., & Cabanillas, A. M. (2007). The ZFHX1A gene is differentially autoregulated by its isoforms. Biochemical and Biophysical Research Communications, 360, 621–626.PubMed
149.
Liu, Y., Costantino, M. E., Montoya-Durango, D., Higashi, Y., Darling, D. S., & Dean, D. C. (2007). The zinc finger transcription factor ZFHX1A is linked to cell proliferation by Rb-E2F1. Biochemical Journal, 408, 79–85.PubMed
150.
Anose, B. M., LaGoo, L., & Schwendinger, J. (2008). Characterization of androgen regulation of ZEB-1 and PSA in 22RV1 prostate cancer cells. Advances in Experimental Medicine and Biology, 617, 541–546.PubMed
151.
Krishnamachary, B., Zagzag, D., Nagasawa, H., Rainey, K., Okuyama, H., Baek, J. H., et al. (2006). Hypoxia-inducible factor-1-dependent repression of E-cadherin in von Hippel-Lindau tumor suppressor-null renal cell carcinoma mediated by TCF3, ZFHX1A, and ZFHX1B. Cancer Research, 66, 2725–2731.PubMed
152.
Singh, M., Spoelstra, N. S., Jean, A., Howe, E., Torkko, K. C., Clark, H. R., et al. (2008). ZEB1 expression in type I vs type II endometrial cancers: a marker of aggressive disease. Modern Pathology, 21, 912–923.PubMed
153.
Spoelstra, N. S., Manning, N. G., Higashi, Y., Darling, D., Singh, M., Shroyer, K. R., et al. (2006). The transcription factor ZEB1 is aberrantly expressed in aggressive uterine cancers. Cancer Research, 66, 3893–3902.PubMed
154.
Chua, H. L., Bhat-Nakshatri, P., Clare, S. E., Morimiya, A., Badve, S., & Nakshatri, H. (2006). NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2. Oncogene, 26, 711–724.PubMed
155.
Aigner, K., Descovich, L., Mikula, M., Sultan, A., Dampier, B., Bonne, S., et al. (2007). The transcription factor ZEB1 (deltaEF1) represses Plakophilin 3 during human cancer progression. FEBS Lett, 581, 1617–1624.PubMed
156.
Aigner, K., Dampier, B., Descovich, L., Mikula, M., Sultan, A., Schreiber, M., et al. (2007). The transcription factor ZEB1 (deltaEF1) promotes tumour cell dedifferentiation by repressing master regulators of epithelial polarity. Oncogene, 26, 6979–6988.PubMed
157.
Kleer, C. G., Zhang, Y., Pan, Q., & Merajver, S. D. (2004). WISP3 (CCN6) is a secreted tumor-suppressor protein that modulates IGF signaling in inflammatory breast cancer. Neoplasia, 6, 179–185.PubMed
158.
Zhang, Y., Pan, Q., Zhong, H., Merajver, S. D., & Kleer, C. G. (2005). Inhibition of CCN6 (WISP3) expression promotes neoplastic progression and enhances the effects of insulin-like growth factor-1 on breast epithelial cells. Breast Cancer Res, 7, R1080–1089.PubMed
159.
Kleer, C. G., Zhang, Y., & Merajver, S. D. (2007). CCN6 (WISP3) as a new regulator of the epithelial phenotype in breast cancer. Cells Tissues Organs, 185, 95–99.PubMed
160.
Ohira, T., Gemmill, R. M., Ferguson, K., Kusy, S., Roche, J., Brambilla, E., et al. (2003). WNT7a induces E-cadherin in lung cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 100, 10429–10434.PubMed
161.
Park, S. M., Gaur, A. B., Lengyel, E., & Peter, M. E. (2008). The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes and Development, 22, 894–907.PubMed
162.
Oving, I. M., & Clevers, H. C. (2002). Molecular causes of colon cancer. European Journal of Clinical Investigation, 32, 448–457.PubMed
163.
Behrens, J. (2005). The role of the Wnt signalling pathway in colorectal tumorigenesis. Biochemical Society Transactions, 33, 672–675.PubMed
164.
Bienz, M., & Clevers, H. (2000). Linking colorectal cancer to Wnt signaling. Cell, 103, 311–320.PubMed
165.
Hlubek, F., Spaderna, S., Schmalhofer, O., Jung, A., Kirchner, T., & Brabletz, T. (2007). Wnt/FZD signaling and colorectal cancer morphogenesis. Frontiers in Bioscience, 12, 458–470.PubMed
166.
Kinzler, K. W., & Vogelstein, B. (1996). Lessons from hereditary colorectal cancer. Cell, 87, 159–170.PubMed
167.
de Santa Barbara, P., van den Brink, G. R., & Roberts, D. J. (2003). Development and differentiation of the intestinal epithelium. Cellular and Molecular Life Sciences, 60, 1322–1332.PubMed
168.
Sancho, E., Batlle, E., & Clevers, H. (2003). Live and let die in the intestinal epithelium. Current Opinion in Cell Biology, 15, 763–770.PubMed
169.
Brabletz, T., Jung, A., Reu, S., Porzner, M., Hlubek, F., Kunz-Schughart, L., et al. (2001). Variable beta-catenin expression in colorectal cancer indicates a tumor progression driven by the tumor environment. Proceedings of the National Academy of Sciences of the United States of America, 98, 10356–10361.PubMed
170.
Brabletz, T., Jung, A., & Kirchner, T. (2002). Beta-catenin and the morphogenesis of colorectal cancer. Virchows Archiv, 441, 1–11.PubMed
171.
Ueno, H., Mochizuki, H., Hatsuse, K., Hase, K., & Yamamoto, T. (2000). Indicators for treatment strategies of colorectal liver metastases. Annals of Surgery, 231, 59–66.PubMed
172.
Hlubek, F., Jung, A., Kotzor, N., Kirchner, T., & Brabletz, T. (2001). Expression of the invasion factor laminin g2 in colorectal carcinomas is regulated by b-catenin. Cancer Research, 61, 8089–8093.PubMed
173.
Mariadason, J. M., Bordonaro, M., Aslam, F., Shi, L., Kuraguchi, M., Velcich, A., et al. (2001). Down-regulation of beta-catenin TCF signaling is linked to colonic epithelial cell differentiation. Cancer Research, 61, 3465–3471.PubMed
174.
Naishiro, Y., Yamada, T., Takaoka, A. S., Hayashi, R., Hasegawa, F., Imai, K., et al. (2001). Restoration of epithelial cell polarity in a colorectal cancer cell line by suppression of beta-catenin/T-cell factor 4-mediated gene transactivation. Cancer Research, 61, 2751–2758.PubMed
175.
Brabletz, T., Jung, A., Spaderna, S., Hlubek, F., & Kirchner, T. (2005). Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression. Nature Reviews Cancer, 5, 744–749.PubMed
176.
Tetsu, O., & McCormick, F. (1999). Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells [In Process Citation]. Nature, 398, 422–426.PubMed
177.
Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R., et al. (1999). The cyclin D1 gene is a target of the beta-catenin/LEF-1 pathway. Proceedings of the National Academy of Sciences of the United States of America, 96, 5522–5527.PubMed
178.
He, T. C., Sparks, A. B., Rago, C., Hermeking, H., Zawel, L., da Costa, L. T., et al. (1998). Identification of c-MYC as a target of the APC pathway [see comments]. Science, 281, 1509–1512.PubMed
179.
Zhang, T., Otevrel, T., Gao, Z., Ehrlich, S. M., Fields, J. Z., & Boman, B. M. (2001). Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. Cancer Research, 61, 8664–8667.PubMed
180.
Yamada, T., Takaoka, A. S., Naishiro, Y., Hayashi, R., Maruyama, K., Maesawa, C., et al. (2000). Transactivation of the multidrug resistance 1 gene by T-cell factor 4/beta-catenin complex in early colorectal carcinogenesis. Cancer Research, 60, 4761–4766.PubMed
181.
Fodde, R., & Brabletz, T. (2007). Wnt/beta-catenin signaling in cancer stemness and malignant behavior. Current Opinion in Cell Biology, 19, 150–158.PubMed
182.
Stemmer, V., de Craene, B., Berx, G., & Behrens, J. (2008). Snail promotes Wnt target gene expression and interacts with beta-catenin. Oncogene, 27, 5075–5080.PubMed
183.
Roy, H. K., Smyrk, T. C., Koetsier, J., Victor, T. A., & Wali, R. K. (2005). The transcriptional repressor SNAIL is overexpressed in human colon cancer. Digestive Diseases and Sciences, 50, 42–46.PubMed
184.
Conacci-Sorrell, M., Simcha, I., Ben-Yedidia, T., Blechman, J., Savagner, P., & Ben-Ze’ev, A. (2003). Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. Journal of Cell Biology, 163, 847–857.PubMed
185.
Shioiri, M., Shida, T., Koda, K., Oda, K., Seike, K., Nishimura, M., et al. (2006). Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. British Journal of Cancer, 94, 1816–1822.PubMed
186.
Peinado, H., Portillo, F., & Cano, A. (2004). Transcriptional regulation of cadherins during development and carcinogenesis. International Journal of Developmental Biology, 48, 365–375.PubMed
187.
Hlubek, F., Brabletz, T., Budczies, J., Pfeiffer, S., Jung, A., & Kirchner, T. (2007). Heterogeneous expression of Wnt/beta-catenin target genes within colorectal cancer. International Journal of Cancer, 121, 1941–1948.
188.
Spaderna, S., Schmalhofer, O., Hlubek, F., Berx, G., Eger, A., Merkel, S., et al. (2006). A transient, EMT-linked loss of basement membranes indicates metastasis and poor survival in colorectal cancer. Gastroenterology, 131, 830–840.PubMed
189.
Bates, R. C., & Mercurio, A. M. (2003). Tumor necrosis factor-alpha stimulates the epithelial-to-mesenchymal transition of human colonic organoids. Molecular Biology of the Cell, 14, 1790–1800.PubMed
190.
Jungck, M., Grunhage, F., Spengler, U., Dernac, A., Mathiak, M., Caspari, R., et al. (2004). E-cadherin expression is homogeneously reduced in adenoma from patients with familial adenomatous polyposis: an immunohistochemical study of E-cadherin, beta-catenin and cyclooxygenase-2 expression. Int J Colorectal Dis, 19, 438–445.PubMed
191.
Dohadwala, M., Luo, J., Zhu, L., Lin, Y., Dougherty, G. J., Sharma, S., et al. (2001). Non-small cell lung cancer cyclooxygenase-2-dependent invasion is mediated by CD44. Journal of Biological Chemistry, 276, 20809–20812.PubMed
192.
Dohadwala, M., Batra, R. K., Luo, J., Lin, Y., Krysan, K., Pold, M., et al. (2002). Autocrine/paracrine prostaglandin E2 production by non-small cell lung cancer cells regulates matrix metalloproteinase-2 and CD44 in cyclooxygenase-2-dependent invasion. Journal of Biological Chemistry, 277, 50828–50833.PubMed
193.
Tsujii, M., Kawano, S., & DuBois, R. N. (1997). Cyclooxygenase-2 expression in human colon cancer cells increases metastatic potential. Proceedings of the National Academy of Sciences of the United States of America, 94, 3336–3340.PubMed
194.
Longo, K. A., Kennell, J. A., Ochocinska, M. J., Ross, S. E., Wright, W. S., & MacDougald, O. A. (2002). Wnt signaling protects 3T3-L1 preadipocytes from apoptosis through induction of insulin-like growth factors. Journal of Biological Chemistry, 277, 38239–38244.PubMed
195.
Dannenberg, A. J., & Zakim, D. (1999). Chemoprevention of colorectal cancer through inhibition of cyclooxygenase-2. Seminars in Oncology, 26, 499–504.PubMed
196.
Shao, J., Jung, C., Liu, C., & Sheng, H. (2005). Prostaglandin E2 Stimulates the beta-catenin/T cell factor-dependent transcription in colon cancer. Journal of Biological Chemistry, 280, 26565–26572.PubMed
197.
Jin, T., George Fantus, I., & Sun, J. (2008). Wnt and beyond Wnt: Multiple mechanisms control the transcriptional property of beta-catenin. Cellular Signalling, 20, 1697–1704.PubMed
198.
Spaderna, S., Schmalhofer, O., Wahlbuhl, M., Dimmler, A., Bauer, K., Sultan, A., et al. (2008). The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Research, 68, 537–544.PubMed
199.
Barsky, S. H., Siegal, G. P., Jannotta, F., & Liotta, L. A. (1983). Loss of basement membrane components by invasive tumors but not by their benign counterparts. Laboratory Investigation, 49, 140–147.PubMed
200.
Wodarz, A., & Nathke, I. (2007). Cell polarity in development and cancer. Nat Cell Biol, 9, 1016–1024.PubMed
201.
Marazuela, M., & Alonso, M. A. (2004). Expression of MAL and MAL2, two elements of the protein machinery for raft-mediated transport, in normal and neoplastic human tissue. Histology and Histopathology, 19, 925–933.PubMed
202.
Woodhouse, E., Hersperger, E., & Shearn, A. (1998). Growth, metastasis, and invasiveness of Drosophila tumors caused by mutations in specific tumor suppressor genes. Development Genes and Evolution, 207, 542–550.PubMed
203.
Baskerville, S., & Bartel, D. P. (2005). Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA, 11, 241–247.PubMed
204.
Lu, J., Getz, G., Miska, E. A., Alvarez-Saavedra, E., Lamb, J., Peck, D., et al. (2005). MicroRNA expression profiles classify human cancers. Nature, 435, 834–838.PubMed
205.
Cano, A., & Nieto, M. A. (2008). Non-coding RNAs take centre stage in epithelial-to-mesenchymal transition. Trends in Cell Biology, 18, 357–359.PubMed
Metadaten
Titel
E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer
verfasst von
Otto Schmalhofer
Simone Brabletz
Thomas Brabletz
Publikationsdatum
01.06.2009
Verlag
Springer US
Erschienen in
Cancer and Metastasis Reviews / Ausgabe 1-2/2009
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-008-9179-y

Weitere Artikel der Ausgabe 1-2/2009

Cancer and Metastasis Reviews 1-2/2009 Zur Ausgabe

OriginalPaper

The mitotic functions of integrin-linked kinase

Acknowledgments

Biographies

OriginalPaper

Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion

OriginalPaper

EMT, the cytoskeleton, and cancer cell invasion

EditorialNotes

Preface

OriginalPaper

Kinesin motor proteins as targets for cancer therapy

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

23.04.2024 Medikamente in Schwangerschaft und Stillzeit Nachrichten

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise