Epithelial-mesenchymal transitions in tumor progression

Nature Reviews Cancer

Volumn 2, Issue 6, 2002, Pages 442-454

  Their, Jean Paul ^a  

^a CNRS   (France)

Author keywords

[No Author keywords available]

Indexed keywords

GEFITINIB; PROTEIN TYROSINE KINASE; SEMAXANIB; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TRASTUZUMAB; UVOMORULIN;

BREAST CARCINOMA; CANCER STAGING; CANCER SURVIVAL; CELL KINETICS; CLINICAL TRIAL; CULTURE MEDIUM; DOWN REGULATION; DRUG TARGETING; ENZYME ACTIVATION; EPITHELIUM CELL; GASTRULATION; GENE MUTATION; GENE REPRESSION; GENETIC TRANSCRIPTION; HUMAN; LUNG SMALL CELL CANCER; MESENCHYME CELL; MOLECULAR DYNAMICS; MOLECULAR MECHANICS; MORPHOGENESIS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TUMOR DIFFERENTIATION; TUMOR GROWTH; ANIMAL; CELL ADHESION; CELL DIFFERENTIATION; CELL MOTION; CELL TRANSFORMATION; DISEASE COURSE; EPITHELIUM; MESODERM; METABOLISM; NEOPLASM; ONCOGENE; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; PRENATAL DEVELOPMENT;

ANIMALS; CELL ADHESION; CELL DIFFERENTIATION; CELL MOVEMENT; CELL TRANSFORMATION, NEOPLASTIC; DISEASE PROGRESSION; EPITHELIUM; HUMANS; MESODERM; MORPHOGENESIS; NEOPLASMS; ONCOGENES; RECEPTOR PROTEIN-TYROSINE KINASES;

EID: 0036595629     PISSN: 1474175X     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrc822     Document Type: Review

References (164)

1. Lillie, F. R. The Development of the Chick (Henry Holt and Co, New York, 1908).
2. Trelstad, R. L., Hay, E. D. & Revel, J. D. Cell contact during early morphogenesis in the chick embryo. Dev. Biol. 16, 78-106 (1967).
3. Hay, E. D. in Epithelial-Mesenchymal Interactions (eds Fleischmajer, R. & Billingham, R. E.) 31-35 (Williams & Wilkins, Baltimore, 1968).
4. Greenburg, G. & Hay, E. D. Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells. J. Cell Biol. 95, 333-339 (1982). The first approach to describe the analysis of EMT in epithelial tissues.
5. Stoker, M. & Perryman, M. An epithelial scatter factor released by embryo fibroblasts. J. Cell Sci. 77, 209-223 (1985). The first in vitro study that revealed a scatter-factor activity in epithelial cells.
6. Stoker, M., Gherardi, E., Perryman, M. & Gray, J. Scatter factor is a fibroblast-derived modulator of epithelial cell mobility. Nature 327, 239-242 (1987).
7. Nakamura, T. et al. Molecular cloning and expression of human hepatocyte growth factor, Nature 342, 440-443 (1989).
8. Naldini, L. et al. Scatter factor and hepatocyte growth factor are indistinguishable ligands for the MET receptor. EMBO J. 10, 2867-2878 (1991).
9. Weidner, K. M. et al. Molecular characteristics of HGF-SF and its role in cell motility and invasion. Exs. 65, 311-328 (1993).
10. Wick, M. R. & Swanson, P. E. Carcinosarcomas: current perspectives and an historical review of nosological concepts. Semin. Diagn. Pathol. 10, 118-127 (1993).
11. Thompson, L., Chang, B. & Barsky, S. H. Monoclonal origins of malignant mixed tumors (carcinosarcomas). Evidence for a divergent histogenesis. Am. J Surg. Pathol. 20, 277-285 (1996).
12. Torenbeek, R., Hermsen, M. A., Meijer, G. A., Baak, J. P. & Meijer, C. J. Analysis by comparative genomic hybridization of epithelial and spindle cell components in sarcomatoid carcinoma and carcinosarcoma: histogenetic aspects. J Pathol. 189, 338-343 (1999).
13. Mayall, F., Rutty, K., Campbell, F. & Goddard, H. p53 immunostaining suggests that uterine carcinosarcomas are monoclonal. Histopathology 24, 211-214 (1994).
14. Iascone, C. & Barreca, M. Carcinosarcoma and pseudosarcoma of the esophagus: two names, one disease: comprehensive review of the literature. World J. Surg 23, 153-157 (1999).
15. Gilbert, S. F. Developmental Biology (Sinauer Associates Inc., Sunderland, Massachusetts, 1997).
16. Stern, C. & Ingham, P. Gastrulation (The Company of Biologists Limited, Cambridge, UK, 1992).
17. Takeichi, M. Morphogenetic roles of classic cadherins. Curr Opin. Cell Biol. 7, 619-627 (1995).
18. Kemler, R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 9, 317-321 (1993)
19. Tepass, U., Truong, K., Godt, D., Ikura, M. & Peifer, M. Cadherins in embryonic and neural morphogenesis. Nature Rev. Mol. Cell Biol. 1, 91-100 (2000).
20. Adams, C. L. & Nelson W. J. Cytomechanics of cadherin-mediated cell-cell adhesion. Curr. Opin. Cell Biol. 10, 572-577 (1998).
21. Kowalczyk, A. P., Bornslaeger, E. A., Norvell, S. M., Palka, H. L. & Green, K. J. Desmosomes: intercellular adhesive junctions specialized for attachment of intermediate filaments. Int. Rev. Cytol. 185, 237-302 (1999).
22. Garrod, D., Chidgey, M. & North, A. Desmosomes: differentiation, development, dynamics and disease. Curr Opin. Cell Biol. 8, 670-678 (1996).
23. Imhof, B. A., Vollmers, H. P., Goodman, S. L. & Birchmeier, W. Cell-cell interaction and polanty of epithelial cells: specific perturbation using a monoclonal antibody. Cell 35, 667-675
24. Damjanov, I., Damjanov, A. & Damsky, C. H. Developmentally regulated expression of the cell-cell adhesion glycoprotein cell-CAM 120/80 in peri-implantation mouse embryos and extraembryonic membranes. Dev. Biol. 116, 194-202 (1986).
25. Veltmaat, J. M. et al. Snail is an immediate early target gene of parathyroid hormone related peptide signaling in parietal endoderm formation. Int. J. Dev. Biol. 44, 297-307 (2000).
26. Tepass, U. et al. Shotgun encodes Drosophila E-cadherin and is preferentially required during cell rearrangement in the neurectoderm and other morphogenetically active epithelia. Genes Dev. 10, 672-685 (1996).
27. Edelman, G. M., Gallin, W. J., Delouvee, A., Cunningham, B A. & Thiery, J. P. Early epochal maps of two different cell adhesion molecules. Proc. Natl. Acad Sci. USA 80, 4384-4388 (1983). The first demonstration of the downregulation of E-cadherin in EMT during gastrulation in the chick.
28. Burdsal, C. A., Damsky, C. H. & Pedersen, R. A. The role of E-cadherin and integrins in mesoderm differentiation and migration at the mammalian primitive steak Development 118, 829-844 (1993).
29. Kuure, S., Vuolteenaho, R. & Vainio, S. Kidney morphogenesis: cellular and molecular regulation. Mech. Dev. 92, 31-45 (2000).
30. Hatta, K., Takagi, S., Fujisawa, H. & Takeichi, M. Spatial and temporal expression pattern of N-cadherin cell adhesion molecules correlated with morphogenetic processes of chicken embryos. Dev. Biol. 120, 215-227 (1987).
31. Duband, J. L. et al. Adhesion molecules during somitogenesis in the avian embryo. J. Cell Biol. 104, 1361-1374 (1987).
32. Frixen, U H. et al. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells J. Cell Biol. 113, 173-185 (1991). One of the first extensive reports to correlate the loss of E-cadherin expression and dedifferentiation and invasive properties of carcinoma cells.
33. Behrens, J., Mareel, M. M., Van Roy, F. M. & Birchmeier, W. Dissecting tumor cell invasion: epithelial cells acquire invasive properties after the loss of uvomorulin-mediated cell-cell adhesion. J. Cell Biol. 108, 2435-2447 (1989).
34. Chen, W. C. & Obrink, B. Cell-cell contacts mediated by E-cadherin (uvomorulin) restrict invasive behavior of L-cells J. Cell Biol. 114, 319-327 (1991).
35. Kim, J. B. et al. N-cadherin extracellular repeat 4 mediates epithelial to mesenchymal transition and increased motility J. Cell Biol. 151, 1193-1206 (2000).
36. Navarro, P. et al. A role for the E-cadherin cell-cell adhesion molecule during tumor progression of mouse epidermal carcinogenesis. J. Cell Biol. 115, 517-533 (1991).
37. Vleminckx, K., Vakaet, L. Jr, Mareel, M., Fiers, W. & van Roy, F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell 66, 107-119 (1991).
38. Birchmeier, W. & Behrens, J. Cadherin expression in carcinomas: role in the formation of cell junctions and the prevention of invasiveness. Biochim. Biophys. Acta 1198, 11-26 (1994).
39. Hirohashi, S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am. J. Pathol. 153, 333-339 (1998).
40. Berx, G. et al. E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBO J. 14, 6107-6115 (1995). The first evidence for somatic mutations in the E-cadherin gene in a significant proportion of lobular breast cancer, and the first demonstration that E-cadherin is a tumour suppressor. This finding has allowed the re-interpretation of the classification of lobular cancers.
41. Risinger, J. I., Berchuck, A., Kohler, M. F. & Boyd, J. Mutations of the E-cadherin gene in human gynecologic cancers. Nature Genet. 7, 98-102 (1994).
42. Yoshiura, K. et al. Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas, Proc. Natl Acad. Sci. USA 92, 7416-7419 (1995).
43. Hennig, G. et al. Progression of carcinoma cells is associated with alterations in chromatin structure and factor binding at the E-cadherin promoter in vivo. Oncogene 11, 475-484 (1995).
44. Hennig, G., Lowrick, O., Birchmeier, W. & Behrens, J. Mechanisms identified in the transcriptional control of epithelial gene expression. J. Biol. Chem. 271, 595-602 (1996).
45. Hajra, K. M., Ji, X. & Fearon, E. R. Extinction of E-cadhedrin expression in breast cancer via a dominant repression pathway acting on proximal promoter elements. Oncogene 15, 7274-7279 (1999).
46. Rodrigo, I., Cato, A. C. & Cano, A. Regulation of E-cadherin gene expression during tumor progression: the role of a new Ets-binding site and the E-pal element. Exp. Cell Res. 248, 358-371 (1999).
47. Tamura, G. et al. E-cadherin gene promoter hypermethylation in primary human gastric carcinomas. J. Natl Cancer Inst. 92, 569-573 (2000).
48. Batlle, E. et al. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nature Cell Biol. 2, 84-89 (2000). Shows that Snail acts as a transcriptional repressor by binding to the E-boxes of the E-cadherin promoter. Snail might become a valuable target for the restoration of the differentiated phenotype in carcinoma.
49. Cano, A. et al. The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nature Cell Biol. 2, 76-83 (2000). An important contribution to the molecular analysis of mechanisms that govern EMT in embryos and in carcinoma. Snail can be considered a 'master gene' in the conversion from the epithelial to fibroblastic state.
50. Leptin, M. Twist and Snail as positive and negative regulators during Drosophlia mesoderm development. Genes Dev. 5, 1568-1576 (1991).
51. Oda, H., Tsukita, S. & Takeichi, M. Dynamic behavior of the cadherin-based cell-cell adhesion system during Drosophila gastrulation. Dev. Biol. 203, 435-450 (1998).
52. Hemavathy K., Ashraf, S. I. & lp, Y. T. Snail/Slug family of repressors: slowly going into the fast lane of development and cancer. Gene 257, 1-12 (2000).
53. Nieto, M. A., Sargent, M. G., Wilkinson, D. G. & Cooke, J. Control of cell behavior during vertebrate development by Slug, a zinc finger gene. Science 264, 835-839 (1994). The first evidence that embryonic EMT is controlled by a zinc-finger transcriptional repressor that belongs to the Snail family.
54. Linker, C., Bronner-Fraser, M. & Mayor, R. Relationship between gene expression domains of Xsnail, Xslug, and Xtwist and cell movement in the prospective neural crest of Xenopus. Dev. Biol. 224, 215-225 (2000)
55. Manzanares, M., Locascio, A. & Nieto, M. A. The increasing complexity of the Snail gene superfamily in metazoan evolution. Trends Genet. 17, 178-181 (2001)
56. Carl, T. F., Dufton, C., Hanken, J. & Klymkowsky, M. W. Inhibition of neural crest migration in Xenopus using antisense slug RNA. Dev. Biol. 213, 101-115 (1999).
57. LaBonne, C. & Bronner-Fraser, M. Snail-related transcriptional repressors are required in Xenopus for both the induction of the neural crest and its subsequent migration. Dev. Biol. 221, 195-205 (2000).
58. Nieto, M. A. The early steps of neural crest development. Mech. Dev 105, 27-35 (2001).
59. del Barrio, M. G. & Nieto, M. A. Overexpression of Snail family members highlights their ability to promote chick neural crest formation. Development 129, 1583-1593 (2002).
60. Carver, E. A., Jiang, R., Lan, Y., Orim, K. F. & Gridley, T. The mouse Snail gene encodes a key regulator of the epithelial-mesenchymal transition. Mol. Cell Biol. 21, 8184-8188 (2001).
61. Comijn, J. et al. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol. Cell 7, 1267-1278 (2001). A detailed analysis of Sip1, which acts as a strong transcriptional repressor of E-cadherin. Sip1 is controlled both by Tgf-β and tyrosine kinase receptor signalling.
62. Perez-Moreno, M. A. et al. A new role for E12/E47 in the repression of E-cadherin expression and epithelial-mesenchymal transitions. J. Biol. Chem. 17, 17 (2001).
63. Blanco, M. J. et al. Correlation of Snail expression with histological grade and lymph node in breast carcinomas. Oncogene (in the press).
64. Yokoyama, K. et al. Reverse correlation of E-cadherin and Snail expression in oral squamous cell carcinoma cells in vitro. Oral Oncol. 37, 65-71 (2001).
65. De Medina, S. G. et al. Relationship between E-cadherin and fibroblast growth factor receptor-2β expression in bladder carcinomas. Oncogene 18, 5722-5726 (1999)).
66. Berx, G., Becker, K. F., Hofler, H. & van Roy, F. Mutations of the human E-cadherin (CDHI) gene. Hum. Mutat. 12, 226-237 (1998).
67. Oda, T. et al. E-cadherin gene mutations in human gastric carcinoma cell lines. Proc. Natl Acad. Sci. USA 91, 1858-1862 (1994).
68. Becker, K. F. et al. E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 54, 3845-3852 (1994). The first study that shows that somatic mutations in the E-cadherin gene contribute to the progression of diffuse gastric carcinomas.
69. Guilford, P. et al. E-cadherin germ-line mutations in familial gastric cancer. Nature 392, 402-405 (1998). The first report to describe E-cadherin germ-line mutations in a large kindred from New Zealand, which was found to be responsible for the early onset of high-grade diffuse gastric tumours.
70. Guilford, P. J. et al. E-cadherin germline mutations define an inherited cancer syndrome dominated by diffuse gastric cancer. Hum. Mutat. 14, 249-255 (1999).
71. Richards, F. M. et al. Germline E-cadherin gene (CDHI) mutations predispose to familial gastric cancer and colorectal cancer. Hum. Mol. Genet 8, 607-610 (1999).
72. Keller, G. et al. Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation. Am. J. Pathol. 155, 337-342 (1999).
73. Perl, A. K., Wilgenbus, P., Dahl, U., Semb, H. & Christofori, G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392, 190-193 (1998).
74. Reichmann, E. et al. Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion. Cell 71, 1103-1116 (1992).
75. Eger, A., Stockinger, A., Schaffhauser, B., Beug, H. & Foisner, R. Epithelial mesenchymal transition by c-Fos estrogen receptor activation involves nuclear translocation of β-catenin and upregulation of β-catenin/lymphoid enhancer binding factor-1 transcriptional activity. J. Cell Biol. 148, 173-188 (2000).
76. Gottardi, C. J., Wong, E. & Gumbiner, B. M. E-cadherin suppresses cellular transformation by inhibiting β-catenin signaling in an adhesion-independent manner. J. Cell Biol. 153, 1049-1060 (2001).
77. Stockinger, A., Eger, A., Wolf, J., Beug, H. & Foisner, R. E-cadherin regulates cell growth by modulating proliferation-dependent β-catenin transcriptional activity. J. Cell Biol. 154, 1185-1196 (2001).
78. Logan, C. Y., Miller, J. R., Ferkowicz, M. J. & McClay, D. R. Nuclear β-catenin is required to specify vegetal cell fates in the sea urchin embryo. Development 126, 345-357 (1999).
79. Huelsken, J., Vogel, R., Erdmann, B., Cotsarelis, G. & Birchmeier, W. β-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105, 533-545 (2001).
80. Huelsken, J. et al. Requirement for β-catenin in anterior-posterior axis formation in mice. J Cell Biol. 148, 567-578 (2000).
81. Novak, A. et al. Cell adhesion and the integrin-linked kinase regulate the LEF-1 and β-catenin signaling pathways. Proc. Natl Acad. Sci. USA 95, 4374-4379 (1998).
82. Morali, O. G. et al. IGF-II induces rapid β-catenin relocation to the nucleus during epithelium to mesenchyme transition. Oncogene 20, 4942-4950 (2001).
83. Kim, K., Pang, K. M., Evans, M. & Hay, E. D. Overexpression of β-catenin induces apoptosis independent of its transactivation function with LEF-1 or the involvement of major G1 cell cycle regulators. Mol. Biol. Cell. 11, 3509-3523 (2000).
84. Trusolino, L. & Comoglio, P. M. Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nature Rev. Cancer 2, 289-300 (2002).
85. Schmidt, C. et al. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 373, 699-702 (1995). The first demonstration of the function of Hgf in vivo during embryogenesis in liver and placental development.
86. Bladt, F., Riethmacher, D., Isenmann, S., Aguzzi, A. & Birchmeier, C. Essential role for the c-Met receptor in the migration of myogenic precursor cells into the limb bud. Nature 376, 768-771 (1995)
87. Bottaro, D. P. et al. Identification of the hepatocyte growth factor receptor as the c-Met proto-oncogene product. Science 251, 802-804 (1991).
88. Weidner, K. M., Sachs, M. & Birchmeier, W. The Met receptor tyrosine kinase transduces motility, proliferation, and morphogenic signals of scatter factor/hepatocyte growth factor in epithelial cells. J. Cell Biol. 121, 145-154 (1993).
89. Ponzetto, C. et al. A multifunctional docking site mediates signaling and transformation by the hepatocyte growth factor/scatter factor receptor family. Cell 77, 261-271 (1994). The first description of the multifunctional docking site for the Met receptor that recognizes SH2-containing adaptor and effector proteins that are involved in diverse functions.
90. Comoglio, P. M. Pathway specificity for Met signalling. Nature Cell Biol. 3, E161-E162 (2001).
91. Furge, K. A., Zhang, Y. W. & Vande Woude, G. F. Met receptor tyrosine kinase: enhanced signaling through adapter proteins. Oncogene 19, 5582-5589 (2000).
92. Itoh, M. et al. Role of Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation. Mol. Cell. Biol. 20, 3695-3704 (2000).
93. Gual, P. et al. Sustained recruitment of phospholipase C-γto Gab1 is required for HGF-induced branching tubulogenesis Oncogene 19, 1509-1518 (2000).
94. Schaeper, U. et al. Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J. Cell Biol, 149, 1419-1432 (2000). A detailed study of the multifunctional adaptor Gab1 and the finding that the tyrosine phosphatase Shp2 is crucial in branching morphogenesis.
95. Petrelli, A. et al. The endophilin-CIN85-CBL complex mediates ligand-dependent downregulation of c-MET Nature 416, 187-190 (2002).
96. Foumier, T. M. et al. Cbl-transforming variants trigger a cascade of molecular alterations that lead to epithelial mesenchymal conversion. Mol. Biol. Cell 11, 3397-3410 (2000).
97. Peschard, P. et al. Mutation of the c-Cb1 TKB domain binding site on the Met receptor tyrosine kinase converts it into a transforming protein. Mol. Cell 8, 995-1004 (2001).
98. Maina, F. et al. Coupling Met to specific pathways results in distinct developmental outcomes. Mol. Cell 8, 1293-1306 (2001). Addresses the multiple functions of Met in development, focusing on the two most important docking sites for the adaptor and effector proteins.
99. Tulasne, D., Paumelle, R., Weidner, K. M., Vandenbunder, B. & Fafeur, V. The multisubstrate docking site of the MET receptor is dispensable for MET-mediated RAS signaling and cell scattering. Mol. Biol. Cell 10, 551-565 (1999).
100. Paumelle, R. et al. Sequential activation of ERK and repression of JNK by scatter factor/hepatocyte growth factor in madin-darby canine kidney epithelial cells. Mol. Biol. Cell 11, 3751-3763 (2000).
101. Boccaccio, C. et al. Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature 391, 285-288 (1998).
102. Di Renzo, M. F. et al. Overexpression of the c-MET/HGF receptor gene in human thyroid carcinomas. Oncogene 7, 2549-2553 (1992).
103. Di Renzo, M. F., Poulsom, R., Olivero, M., Comoglio, P. M. & Lemoine, N. R. Expression of the MET/hepatocyte growth factor receptor in human pancreatic cancer. Cancer Res. 55, 1129-1138 (1995).
104. Di Renzo, M. F. et al. Overexpression and amplification of the MET/HGFreceptor gene during the progression of colorectal cancer. Clin. Cancer Res. 1, 147-154 (1995)
105. Di Renzo, M. F. et al. Somatic mutations of the MET oncogene are selected during metastatic spread of human HNSC carcinomas. Oncogene 19, 1547-1555 (2000).
106. Schmidt, L. et al. Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nature Genet. 16, 68-73 (1997). This recently recognized form of renal carcinoma results from a constitutive activation of the Met receptors by missense mutations in the tyrosine kinase domain.
107. Lee, J. H. et al. A novel germ line juxtamembrane Met mutation in human gastric cancer. Oncogene 19, 4947-4953 (2000).
108. Giordano, S. et al. Different point mutations in the Met oncogene elicit distinct biological properties. FASEB J. 14, 399-406 (2000).
109. Valles, A. M. et al. Acidic fibroblast growth factor is a modulator of epithelial plasticity in a rat bladder carcinoma cell line. Proc. Natl Acad. Sci. USA 87, 1124-1128 (1990).
110. Morali, O. G., Jouneau, A., McLaughlin, K. J., Thiery, J. P. & Larue, L. IGF-II promotes mesoderm formation. Dev. Biol. 227, 133-145 (2000).
111. Khoury, H. et al. Distinct tyrosine autophosphorylation sites mediate induction of epithelial mesenchymal like transition by an activated ErbB2/Neu receptor. Oncogene 20, 788-799 (2001)
112. Meiners, S., Brinkmann, V., Naundorf, H. & Birchmeier, W. Role of morphogenetic factors in metastasis of mammary carcinoma cells. Oncogene 16, 9-20 (1998).
113. Ciruna, B. & Rossant, J. FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. Dev. Cell. 1, 37-49 (2001). Links, for the first time, the signal-transduction pathways of EMT and the determination of the mesodermal lineage in mouse gastrula.
114. Thiery, J. P. & Chopin, D. Epithelial cell plasticity in development and tumor progression. Cancer Metastasis Rev. 18, 31-42 (1999)
115. Boyer, B., Roche, S., Denoyelle, M. & Thiery, J. P. Src and Ras are involved in separate pathways in epithelial cell scattering. EMBO J. 16, 5904-5913 (1997). The first evidence for Slug as a crucial gene in EMT of carcinoma cells.
116. Savagner, P., Yamada, K. M. & Thiery, J. P. The zinc-finger protein slug causes desmosome dissociation, an initial and necessary step for growth factor-induced epithelial-mesenchymal transition. J. Cell Biol. 137, 1403-1419 (1997).
117. Edme, N., Downward, J., Thiery, J. P. & Boyer, B. Involvement of MAPK and Rac in epithelial cell scatterring. J. Cell Sci. (in the press)
118. Sanders, L. C., Matsumura, F., Bokoch, G. M. & de Lanerolle, P. Inhibition of myosin light chain kinase by p21-activated kinase. Science 283, 2083-2085 (1999). Reveals an important regulatory mechanism that controls cell shape in the stationary and motile states. Rho and Rac have an antagonistic function to control actin microfilament dynamics by the phosphorylation of the myosin light chain.
119. Horwitz, A. R. & Parsons, J. T. Cell migration: movin' on. Science 286, 1102-1103 (1999).
120. Hordijk, P. L. et al. Inhibition of invasion of epithelial cells by Tiam1-Rac signaling. Science 278, 1464-1466 (1997).
121. Rottner, K., Hall, A. & Small, J. V. Interplay between Rac and Rho in the control of substrate contact dynamics. Curr. Biol. 9, 640-648 (1999).
122. Price, L. S. & Collard, J. G. Regulation of the cytoskeleton by Rho-family GTPases: implications for tumour cell invasion. Semin. Cancer Biol. 11, 167-173 (2001).
123. Anastasiadis, P. Z. & Reynolds, A. B. Regulation of Rho GTPases by p120-catenin. Curr. Opin. Cell Biol. 13, 604-610 (2001).
124. Fujita, Y. et al. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nature Cell Biol. 4, 222-231 (2002).
125. Muller, T., Choidas, A., Reichmann, E. & Ullrich, A. Phosphorylation and free pool of β-catenin are regulated by tyrosine kinases and tyrosine phosphatases during epithelial cell migration. J. Biol. Chem. 274, 10173-10183 (1999).
126. Jouanneau, J., Moens, G. & Thiery, J. P. The community effect in FGF-1 mediated tumor progression of a rat bladder carcinoma does not involve a direct paracnne signaling. Oncogene 18, 327-333 (1999).
127. Grassi, M., Moens, G., Rousselle, P., Thiery, J. P. & Jouanneau, J. The SFL activity secreted by metastatic carcinoma cells is related to laminin 5 and mediates cell scattering in an integrin-independent manner. J. Cell Sci. 112, 2811-2820 (1999).
128. Kaartinen, V. et al. Abnormal lung development and cleft palate in mice lacking TGF-β3 indicates defects of epithelial-mesenchymal interaction Nature Genet. 11, 415-421 (1995).
129. Romano, L. A. & Runyan, R. B. Slug is an essential target of TGF-β2 signaling in the developing chicken heart. Dev. Biol. 223, 91-102 (2000).
130. Lehmann, K. et al. Raf induces TGF-β production while blocking its apoptotic but not invasive responses: a mechanism leading to increased malignancy in epithelial cells. Genes Dev. 14, 2610-2622 (2000). The discovery of a new mechanism in which the apoptotic function of Tgf-β is abrogated in cells in which the Ras/Raf pathway has been activated.
131. Oft, M. et al. TGF-β1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev. 10, 2462-2477 (1996).
132. Janda, E. et al. Ras and TGF-β cooperatively regulate epithelial cell plasticity and metastasis: dissection of Ras signaling pathways. J. Cell Biol 186, 299-313 (2002).
133. Bhowmick, N. A., Zent, R., Ghiassi, M. McDonnell, M. & Moses, H. L. Integrin-β1 signaling is necessary for transforming growth factor-β activation of p38MAPK and epithelial plasticity J. Biol. Chem. 276, 46707-46713 (2001).
134. Bhowmick, N. A. et al. Transforming growth factor-β1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism. Mol. Biol. Cell 12, 27-36 (2001).
135. Cui, W. et al. TGF-β1 inhibits the formation of benign skin tumors, but enhances progression to invasive spindle carcinomas in transgenic mice. Cell 86, 531-542 (1996).
136. Watanabe, T. et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer N. Engl. J. Med. 344, 1196-1206(2001).
137. Braun, S. & Pantel, K. Biological characteristics of micrometastatic cancer cells in bone marrow. Cancer Metastasis Rev. 18, 75-90 (1999).
138. Braun, S. et al. Lack of effect of adjuvant chemotherapy on the elimination of single dormant tumor cells in bone marrow of high-risk breast cancer patients. J. Clin. Oncol. 18, 80-86 (2000).
139. Braun, S. et al. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N. Engl. J. Med. 342, 525-533 (2000).
140. Slamon, D. J. et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med, 344, 783-792 (2001). One of the first reports providing evidence that a significant benefit is achieved in metastatic breast cancer patients who overexpress ERBB2, by treatment with a monoclonal antibody against this receptor, in combination with chemotherapy.
141. Chan, K. C. et al. Effect of epidermal growth factor receptor tyrosine kinase inhibition on epithelial proliferation in normal and premalignant breast. Cancer Res. 62, 122-128 (2002).
142. Irby, R. B. & Yeatman, T. J. Role of Src expression and activation in human cancer. Oncogene 19, 5636-5642 (2000).
143. Boyer, B., Bourgeois, Y. & Poupon, M. F. Src kinase contributes to the metastatic spread of carcinoma cells. Oncogene 21, 2347-2356 (2002).
144. Lobell, R. B. et al. Evaluation of farnesyl:protein transferase and geranylgeranyl:protein transferase inhibitor combinations in preclinical models. Cancer Res. 61, 8758-8768 (2001).
145. Milella, M. et al. Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia J Clin Invest. 108.851-859 (2001).
146. Tamagnone, L. et al. Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99, 71-80 (1999).
147. Tamagnone, L. & Comoglio, P. M. Signalling by semaphorin receptors: cell guidance and beyond Trends Cell Biol. 10, 377-383 (2000).
148. Hlubek, F., Jung, A., Kotzor, N., Kirchner, T. & Brabletz, T. Expression of the invasion factor laminin-γ2 in colorectal carcinomas is regulated by β-catenin. Cancer Res. 61, 8089-8093 (2001).
149. Wu, C. & Dedhar, S. Integrin-linked kinase (ILK) and its interactors: a new paradigm for the coupling of extracellular matrix to actin cytosketeton and signaling complexes. J. Cell Biol. 155, 505-510 (2001).
150. Zhu, X. et al. A large-scale analysis of mRNAs expressed by primary mesenchyme cells of the sea urchin embryo. Development 128, 2615-2627 (2001).
151. Kiemer, A. K., Takeuchi, K. & Quinlan, M. P. Identification of genes involved in epithelial-mesenchymal transition and tumor progression. Oncogene 20, 6679-6688 (2001).
152. Medico, E. et al. Osteopontin is an autocrine mediator of hepatocyte growth factor-induced invasive growth. Cancer Res 61, 5861-5868 (2001).
153. van't Veer, L. J. et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature 415, 530-536 (2002).
154. Kreidberg, J. A. et al. WT-1 is required for early kidney development. Cell 74, 679-691 (1993).
155. Stark, K., Vainio, S., Vassileva, G. & McMahon, A. P. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372, 679-683 (1994)
156. Dudley, A. T., Lyons, K. M. & Robertson, E. J. A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 9, 2795-2807 (1995).
157. Wynshaw-Boris, A. et al. The role of a single formin isoform in the limb and renal phenotypes of limb deformity. Mol. Med. 3, 372-384 (1997).
158. Brabletz, T., Herrmann, K., Jung, A., Faller, G. & Kirchner, T. Expression of nuclear β-catenin and c-Myc is correlated with tumor size but not with proliferative activity of colorectal adenomas. Am. J. Pathol. 156, 865-870 (2000).
159. Brabletz, T. et al. Variable β-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc. Natl Acad. Sci. USA 98, 10356-10361 (2001).
160. Butler T. P. & Gullino, P. M. Quantification of cell shedding into efferent blood of mammary adenocarcinoma. Cancer Res. 35, 3512-3516 (1975).
161. Pantel, K., Cote, R. J. & Fodstad, O. Detection and clinical importance of micrometastatic disease. J. Natl Cancer Inst. 91, 1113-1124 (1999).
162. Naume, B. et al. Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics. Clin. Cancer Res. 7, 4122-4129 (2001).
163. Putz, E. et al. Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res. 59, 241-248 (1999).
164. Duval, M. Atlas d'embryologie (Masson, Paris. 1879).