Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 7 January 1994:
Vol. 263. no. 5143, pp. 98 - 101
DOI: 10.1126/science.7505952
Prev | Table of Contents | Next

Articles

Science, Vol 263, Issue 5143, 98-101
Copyright © 1994 by American Association for the Advancement of Science

articles

The Met proto-oncogene mesenchymal to epithelial cell conversion

I Tsarfaty, S Rong, JH Resau, S Rulong, PP da Silva, and GF Vande Woude

ABL-Basic Research Program, National Cancer Institute (NCI)-Frederick Cancer Research and Development Center, MD 21702-1201.

Coexpression of the human Met receptor and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), in NIH 3T3 fibroblasts causes the cells to become tumorigenic in nude mice. The resultant tumors display lumen-like morphology, contain carcinoma-like focal areas with intercellular junctions resembling desmosomes, and coexpress epithelial (cytokeratin) and mesenchymal (vimentin) cytoskeletal markers. The tumor cells also display enhanced expression of desmosomal and tight-junction proteins. The apparent mesenchymal to epithelial conversion of the tumor cells mimics the conversion that occurs during embryonic kidney development, suggesting that Met-HGF/SF signaling plays a role in this process as well as in tumors that express both epithelial and mesenchymal markers.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
An Orally Available Small-Molecule Inhibitor of c-Met, PF-2341066, Exhibits Cytoreductive Antitumor Efficacy through Antiproliferative and Antiangiogenic Mechanisms.
H. Y. Zou, Q. Li, J. H. Lee, M. E. Arango, S. R. McDonnell, S. Yamazaki, T. B. Koudriakova, G. Alton, J. J. Cui, P.-P. Kung, et al. (2007)
Cancer Res. 67, 4408-4417
   Abstract »    Full Text »    PDF »
Met, the Hepatocyte Growth Factor Receptor, Localizes to the Nucleus in Cells at Low Density.
S. Pozner-Moulis, D. J. Pappas, and D. L. Rimm (2006)
Cancer Res. 66, 7976-7982
   Abstract »    Full Text »    PDF »
Structural basis of hepatocyte growth factor/scatter factor and MET signalling..
E. Gherardi, S. Sandin, M. V. Petoukhov, J. Finch, M. E. Youles, L.-G. Ofverstedt, R. N. Miguel, T. L. Blundell, G. F. Vande Woude, U. Skoglund, et al. (2006)
PNAS 103, 4046-4051
   Abstract »    Full Text »    PDF »
A Selective Small Molecule Inhibitor of c-Met Kinase Inhibits c-Met-Dependent Phenotypes in Vitro and Exhibits Cytoreductive Antitumor Activity in Vivo.
J. G. Christensen, R. Schreck, J. Burrows, P. Kuruganti, E. Chan, P. Le, J. Chen, X. Wang, L. Ruslim, R. Blake, et al. (2003)
Cancer Res. 63, 7345-7355
   Abstract »    Full Text »    PDF »
In situ activation pattern of Met docking site following renal injury and hypertrophy.
B. Dekel, S. Biton, G. M. Yerushalmi, R. T. Altstock, L. Mittelman, D. Faletto, N. I. Smordinski, and I. Tsarfaty (2003)
Nephrol. Dial. Transplant. 18, 1493-1504
   Abstract »    Full Text »    PDF »
In situ activation pattern of Met docking site following renal injury and hypertrophy.
B. Dekel, S. Biton, G. M. Yerushalmi, R. T. Altstock, L. Mittelman, D. Faletto, N. I. Smordinski, and I. Tsarfaty (2003)
Nephrol. Dial. Transplant. 18, 1493-1504
   Abstract »    Full Text »
Constitutive c-Met Signaling through a Nonautocrine Mechanism Promotes Metastasis in a Transgenic Transplantation Model.
Y. Yu and G. Merlino (2002)
Cancer Res. 62, 2951-2956
   Abstract »    Full Text »    PDF »
Blockage of Tubular Epithelial to Myofibroblast Transition by Hepatocyte Growth Factor Prevents Renal Interstitial Fibrosis.
J. Yang and Y. Liu (2002)
J. Am. Soc. Nephrol. 13, 96-107
   Abstract »    Full Text »    PDF »
Hepatocyte Growth Factor/Scatter Factor Released during Peritonitis Is Active on Mesothelial Cells.
T. Rampino, G. Cancarini, M. Gregorini, P. Guallini, M. Maggio, A. Ranghino, G. Soccio, and A. Dal Canton (2001)
Am. J. Pathol. 159, 1275-1285
   Abstract »    Full Text »
Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models.
B. Cao, Y. Su, M. Oskarsson, P. Zhao, E. J. Kort, R. J. Fisher, L.-M. Wang, and G. F. Vande Woude (2001)
PNAS 98, 7443-7448
   Abstract »    Full Text »    PDF »
In Vivo Molecular Imaging of Met Tyrosine Kinase Growth Factor Receptor Activity in Normal Organs and Breast Tumors.
M. Shaharabany, R. Abramovitch, T. Kushnir, G. Tsarfaty, M. Ravid-Megido, J. Horev, R. Ron, Y. Itzchak, and I. Tsarfaty (2001)
Cancer Res. 61, 4873-4878
   Abstract »    Full Text »    PDF »
HGF regulates tight junctions in new nontumorigenic gastric epithelial cell line.
F. Hollande, E. M. Blanc, J. P. Bali, R. H. Whitehead, A. Pelegrin, G. S. Baldwin, and A. Choquet (2001)
Am J Physiol Gastrointest Liver Physiol 280, G910-G921
   Abstract »    Full Text »    PDF »
Disassociation of Met-Mediated Biological Responses In Vivo: the Natural Hepatocyte Growth Factor/Scatter Factor Splice Variant NK2 Antagonizes Growth but Facilitates Metastasis.
T. Otsuka, J. Jakubczak, W. Vieira, D. P. Bottaro, D. Breckenridge, W. J. Larochelle, and G. Merlino (2000)
Mol. Cell. Biol. 20, 2055-2065
   Abstract »    Full Text »
The von Hippel-Lindau Tumor Suppressor Gene Inhibits Hepatocyte Growth Factor/Scatter Factor-Induced Invasion and Branching Morphogenesis in Renal Carcinoma Cells.
S. Koochekpour, M. Jeffers, P. H. Wang, C. Gong, G. A. Taylor, L. M. Roessler, R. Stearman, J. R. Vasselli, W. G. Stetler-Stevenson, W. G. Kaelin Jr., et al. (1999)
Mol. Cell. Biol. 19, 5902-5912
   Abstract »    Full Text »    PDF »
Hepatocyte Growth Factor and c-MET Are Expressed in Rat Prepuberal Testis.
A. Catizone, G. Ricci, V. Arista, A. Innocenzi, and M. Galdieri (1999)
Endocrinology 140, 3106-3113
   Abstract »    Full Text »
Met-HGF/SF Mediates Growth Arrest and Differentiation in T47D Breast Cancer Cells.
D. Ronen, R. T. Altstock, M. Firon, L. Mittelman, T. Sobe, J. H. Resau, G. F. Vande Woude, and I. Tsarfaty (1999)
Cell Growth Differ. 10, 131-140
   Abstract »    Full Text »
Morphogenetic Effects of Neuregulin (Neu Differentiation Factor) in Cultured Epithelial Cells.
A. Chausovsky, I. Tsarfaty, Z. Kam, Y. Yarden, B. Geiger, and A. D. Bershadsky (1998)
Mol. Biol. Cell 9, 3195-3209
   Abstract »    Full Text »
Activation of Delta F508 CFTR in an epithelial monolayer.
Z. Bebok, C. J. Venglarik, Z. Panczel, T. Jilling, K. L. Kirk, and E. J. Sorscher (1998)
Am J Physiol Cell Physiol 275, C599-C607
   Abstract »    Full Text »    PDF »
Monoclonal antibody P-31 recognizes a novel intermediate filament-associated protein (p250) in rat podocytes.
H. Kurihara, N. Sunagawa, T. Kobayashi, K. Kimura, N. Takasu, and T. Shike (1998)
Am J Physiol Renal Physiol 274, F986-F997
   Abstract »    Full Text »    PDF »
NK1, a Natural Splice Variant of Hepatocyte Growth Factor/Scatter Factor, Is a Partial Agonist In Vivo.
J. L. Jakubczak, W. J. Larochelle, and G. Merlino (1998)
Mol. Cell. Biol. 18, 1275-1283
   Abstract »    Full Text »
Hepatocyte Nuclear Factor 4 Provokes Expression of Epithelial Marker Genes, Acting As a Morphogen in Dedifferentiated Hepatoma Cells.
G. F. Spath and M. C. Weiss (1998)
J. Cell Biol. 140, 935-946
   Abstract »    Full Text »    PDF »
Molecular Genetics of Renal Carcinogenesis.
C. Walker (1998)
Toxicol Pathol 26, 113-120
   Abstract »    PDF »
Diverse tumorigenesis associated with aberrant development in mice overexpressing hepatocyte growth factor/scatter factor.
H. Takayama, W. J. LaRochelle, R. Sharp, T. Otsuka, P. Kriebel, M. Anver, S. A. Aaronson, and G. Merlino (1997)
PNAS 94, 701-706
   Abstract »    Full Text »    PDF »
Concomitant Expression of Hepatocyte Growth Factor/Scatter Factor and the Receptor c-MET in Human Myeloma Cell Lines.
M. Borset, E. Lien, T. Espevik, E. Helseth, A. Waage, and A. Sundan (1996)
J. Biol. Chem. 271, 24655-24661
   Abstract »    Full Text »    PDF »
Hepatocyte Growth Factor Releases Epithelial and Endothelial Cells from Growth Arrest Induced by Transforming Growth Factor-beta1.
J. Taipale and J. Keski-Oja (1996)
J. Biol. Chem. 271, 4342-4348
   Abstract »    Full Text »    PDF »
Conditioned medium from a rat ureteric bud cell line in combination with bFGF induces complete differentiation of isolated metanephric mesenchyme.
I. Karavanova, L. Dove, J. Resau, and A. Perantoni (1996)
Development 122, 4159-4167
   Abstract »    PDF »
GDNF Is Required for Kidney Development and Enteric Innervation.
J.G. Pichel, L. Shen, H.Z. Sheng, A.-C. Granholm, J. Drago, A. Grinberg, E.J. Lee, S.P. Huang, M. Saarma, B.J. Hoffer, et al. (1996)
Cold Spring Harb Symp Quant Biol 61, 445-457
   Abstract »    PDF »
The hepatocyte growth factor/scatter factor (HGF/SF) receptor, met, transduces a morphogenetic signal in renal glomerular fibromuscular mesangial cells.
M Kolatsi-Joannou, A. Woolf, P Hardman, S. White, M Gordge, and R. Henderson (1995)
J. Cell Sci. 108, 3703-3714
   Abstract »    PDF »
Epithelial-mesenchymal conversion of dermatome progenitors requires neural tube-derived signals: characterization of the role of Neurotrophin-3.
G Brill, N Kahane, C Carmeli, D von Schack, Y. Barde, and C Kalcheim (1995)
Development 121, 2583-2594
   Abstract »    PDF »
Two CDC25 homologues are differentially expressed during mouse development.
D Wickramasinghe, S Becker, M. Ernst, J. Resnick, J. Centanni, L Tessarollo, L. Grabel, and P. Donovan (1995)
Development 121, 2047-2056
   Abstract »    PDF »
Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death.
C. Ware, M. Horowitz, B. Renshaw, J. Hunt, D Liggitt, S. Koblar, B. Gliniak, H. McKenna, T Papayannopoulou, B Thoma, et al. (1995)
Development 121, 1283-1299
   Abstract »    PDF »
Autocrine Mechanism for met Proto-oncogene Tumorigenicity.
S. Rong and G.F. Vande Woude (1994)
Cold Spring Harb Symp Quant Biol 59, 629-636
   Abstract »    PDF »
Potent Blockade of Hepatocyte Growth Factor-stimulated Cell Motility, Matrix Invasion and Branching Morphogenesis by Antagonists of Grb2 Src Homology 2 Domain Interactions.
N. Atabey, Y. Gao, Z.-J. Yao, D. Breckenridge, L. Soon, J. V. Soriano, T. R. Burke Jr., and D. P. Bottaro (2001)
J. Biol. Chem. 276, 14308-14314
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)