![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Division of Molecular Medicine and Genetics, Department of Internal Medicine, Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA
Carcinoma cells initiate the metastatic cascade by inserting invasive pseudopodia through breaches in the basement membrane (BM), a specialized barrier of cross-linked, extracellular matrix macromolecules that underlies epithelial cells and ensheaths blood vessels. While BM invasion is the sine qua non of the malignant phenotype, the molecular programs that underlie this process remain undefined. To identify genes that direct BM remodeling and transmigration, we coupled high-resolution electron microscopy with an ex vivo model of invasion that phenocopies the major steps observed during the transition of carcinoma in situ to frank malignancy. Herein, a triad of membrane-anchored proteases, termed membrane type-1, type-2, and type-3 metalloproteinases, are identified as the triggering agents that independently confer cancer cells with the ability to proteolytically efface the BM scaffolding, initiate the assembly of invasive pseudopodia, and propagate transmigration. These studies characterize the first series of gene products capable of orchestrating the entire BM remodeling program that distinguishes the carcinomatous phenotype.
[Keywords: Basement membrane; type IV collagen; matrix metalloproteinases; MT-MMPs; cancer; invasion]
Received May 24, 2006; revised version accepted August 4, 2006.
Supplemental material is available at http://www.genesdev.org.
Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.1451806.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  R. J. Bloom, J. P. George, A. Celedon, S. X. Sun, and D. Wirtz Mapping Local Matrix Remodeling Induced by a Migrating Tumor Cell Using Three-Dimensional Multiple-Particle Tracking Biophys. J., October 15, 2008; 95(8): 4077 - 4088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Agarwal, L. Covic, L. M. Sevigny, N. C. Kaneider, K. Lazarides, G. Azabdaftari, S. Sharifi, and A. Kuliopulos Targeting a metalloprotease-PAR1 signaling system with cell-penetrating pepducins inhibits angiogenesis, ascites, and progression of ovarian cancer Mol. Cancer Ther., September 1, 2008; 7(9): 2746 - 2757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Enderling, N. R. Alexander, E. S. Clark, K. M. Branch, L. Estrada, C. Crooke, J. Jourquin, N. Lobdell, M. H. Zaman, S. A. Guelcher, et al. Dependence of Invadopodia Function on Collagen Fiber Spacing and Cross-Linking: Computational Modeling and Experimental Evidence Biophys. J., September 1, 2008; 95(5): 2203 - 2218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Nyalendo, E. Beaulieu, H. Sartelet, M. Michaud, N. Fontaine, D. Gingras, and R. Beliveau Impaired tyrosine phosphorylation of membrane type 1-matrix metalloproteinase reduces tumor cell proliferation in three-dimensional matrices and abrogates tumor growth in mice Carcinogenesis, August 1, 2008; 29(8): 1655 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-Y. Li, I. Ota, I. Yana, F. Sabeh, and S. J. Weiss Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase Mol. Biol. Cell, August 1, 2008; 19(8): 3221 - 3233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-A. Cho, P. Osenkowski, H. Zhao, S. Kim, M. Toth, K. Cole, A. Aboukameel, A. Saliganan, L. Schuger, R. D. Bonfil, et al. The Inactive 44-kDa Processed Form of Membrane Type 1 Matrix Metalloproteinase (MT1-MMP) Enhances Proteolytic Activity via Regulation of Endocytosis of Active MT1-MMP J. Biol. Chem., June 20, 2008; 283(25): 17391 - 17405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sakurai-Yageta, C. Recchi, G. Le Dez, J.-B. Sibarita, L. Daviet, J. Camonis, C. D'Souza-Schorey, and P. Chavrier The interaction of IQGAP1 with the exocyst complex is required for tumor cell invasion downstream of Cdc42 and RhoA J. Cell Biol., June 16, 2008; 181(6): 985 - 998. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. V. Rozanov, A. Y. Savinov, R. Williams, K. Liu, V. S. Golubkov, S. Krajewski, and A. Y. Strongin Molecular Signature of MT1-MMP: Transactivation of the Downstream Universal Gene Network in Cancer Cancer Res., June 1, 2008; 68(11): 4086 - 4096. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Madsen, L. H. Engelholm, S. Ingvarsen, T. Hillig, R. A. Wagenaar-Miller, L. Kjoller, H. Gardsvoll, G. Hoyer-Hansen, K. Holmbeck, T. H. Bugge, et al. Extracellular Collagenases and the Endocytic Receptor, Urokinase Plasminogen Activator Receptor-associated Protein/Endo180, Cooperate in Fibroblast-mediated Collagen Degradation J. Biol. Chem., September 14, 2007; 282(37): 27037 - 27045. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Atkinson, H. M. Toennies, K. Holmbeck, and R. M. Senior Membrane type 1 matrix metalloproteinase is necessary for distal airway epithelial repair and keratinocyte growth factor receptor expression after acute injury Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L600 - L610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Sun, C. R. Weber, A. Sohail, M. M. Bernardo, M. Toth, H. Zhao, J. R. Turner, and R. Fridman MMP25 (MT6-MMP) Is Highly Expressed in Human Colon Cancer, Promotes Tumor Growth, and Exhibits Unique Biochemical Properties J. Biol. Chem., July 27, 2007; 282(30): 21998 - 22010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Yana, H. Sagara, S. Takaki, K. Takatsu, K. Nakamura, K. Nakao, M. Katsuki, S.-i. Taniguchi, T. Aoki, H. Sato, et al. Crosstalk between neovessels and mural cells directs the site-specific expression of MT1-MMP to endothelial tip cells J. Cell Sci., May 1, 2007; 120(9): 1607 - 1614. [Abstract] [Full Text] [PDF]
|
|
