|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 280, Issue 37, 32468-32479, September 16, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Decorin Evokes Protracted Internalization and Degradation of the Epidermal Growth Factor Receptor via Caveolar Endocytosis*
11
¶2
From the
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, the LifeCell Corporation, Branchburg, New Jersey 08876, and the ¶Cellular Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
Decorin inhibits the epidermal growth factor receptor (EGFR) by down-regulating its tyrosine kinase activity, thereby blocking the growth of a variety of transformed cells and tumor xenografts. In this study we provide evidence that decorin directly binds to the EGFR causing its dimerization, internalization, and ultimately its degradation. Using various pharmacological agents to disrupt clathrin-dependent and -independent endocytosis, we demonstrate that decorin evokes a protracted internalization of the EGFR primarily via caveolar-mediated endocytosis. In contrast to EGF, decorin targets the EGFR to caveolae, but not to early or recycling endosomes. Ultimately, however, both EGF- and decorin-induced pathways converge into late endosomes/lysosomes for final degradation. Thus, we have discovered a novel biological mechanism for decorin that could explain its anti-proliferative and anti-oncogenic mode of action.
Received for publication, April 8, 2005 , and in revised form, June 27, 2005.
* This work was supported in part by National Institutes of Health Grants RO1 CA39481 and RO1 CA47282 and Department of the Army Grant DAMD17-00-1-0425 (to R. V. I.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Both authors contributed equally to this work.
2 To whom correspondence should be addressed: Dept. of Pathology, Anatomy and Cell Biology, Rm. 249 Jefferson Alumni Hall, Thomas Jefferson University, 1020 Locust St., Philadelphia, PA 19107. E-mail: iozzo{at}mail.jci.tju.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Goldoni, A. Humphries, A. Nystrom, S. Sattar, R. T. Owens, D. J. McQuillan, K. Ireton, and R. V. Iozzo Decorin is a novel antagonistic ligand of the Met receptor J. Cell Biol., May 18, 2009; 185(4): 743 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Z. Rappoport and S. M. Simon Endocytic trafficking of activated EGFR is AP-2 dependent and occurs through preformed clathrin spots J. Cell Sci., May 1, 2009; 122(9): 1301 - 1305. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ohno, K. Motojima, T. Okano, and A. Taniguchi Maturation of the Extracellular Matrix and Cell Adhesion Molecules in Layered Co-cultures of HepG2 and Endothelial Cells J. Biochem., May 1, 2009; 145(5): 591 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Zoeller, W. Pimtong, H. Corby, S. Goldoni, A. E. Iozzo, R. T. Owens, S.-Y. Ho, and R. V. Iozzo A Central Role for Decorin during Vertebrate Convergent Extension J. Biol. Chem., April 24, 2009; 284(17): 11728 - 11737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Iacob, J. Cai, M. Tsonis, A. Babwah, C. Chakraborty, R. N. Bhattacharjee, and P. K. Lala Decorin-Mediated Inhibition of Proliferation and Migration of the Human Trophoblast via Different Tyrosine Kinase Receptors Endocrinology, December 1, 2008; 149(12): 6187 - 6197. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K. Wali, D. P. Kunte, J. L. Koetsier, M. Bissonnette, and H. K. Roy Polyethylene glycol-mediated colorectal cancer chemoprevention: roles of epidermal growth factor receptor and Snail Mol. Cancer Ther., September 1, 2008; 7(9): 3103 - 3111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Goldoni, D. G. Seidler, J. Heath, M. Fassan, R. Baffa, M. L. Thakur, R. T. Owens, D. J. McQuillan, and R. V. Iozzo An Antimetastatic Role for Decorin in Breast Cancer Am. J. Pathol., September 1, 2008; 173(3): 844 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Schaefer and R. V. Iozzo Biological Functions of the Small Leucine-rich Proteoglycans: From Genetics to Signal Transduction J. Biol. Chem., August 1, 2008; 283(31): 21305 - 21309. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, A. Pennisi, and S. Yaccoby Role of decorin in the antimyeloma effects of osteoblasts Blood, July 1, 2008; 112(1): 159 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Zafiropoulos, D. Nikitovic, P. Katonis, A. Tsatsakis, N. K. Karamanos, and G. N. Tzanakakis Decorin-Induced Growth Inhibition Is Overcome through Protracted Expression and Activation of Epidermal Growth Factor Receptors in Osteosarcoma Cells Mol. Cancer Res., May 1, 2008; 6(5): 785 - 794. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. W. Wong, S. J. Scales, and D. E. Reilly DNA Internalized via Caveolae Requires Microtubule-dependent, Rab7-independent Transport to the Late Endocytic Pathway for Delivery to the Nucleus J. Biol. Chem., August 3, 2007; 282(31): 22953 - 22963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Y. Fan, H. B. Fernandes, L. Y. J. Zhang, M. R. Hayden, and L. A. Raymond Altered NMDA Receptor Trafficking in a Yeast Artificial Chromosome Transgenic Mouse Model of Huntington's Disease J. Neurosci., April 4, 2007; 27(14): 3768 - 3779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Gellersen, J. Briese, M. Oberndorfer, K. Redlin, A. Samalecos, D.-U. Richter, T. Loning, H.-M. Schulte, and A.-M. Bamberger Expression of the Metastasis Suppressor KAI1 in Decidual Cells at the Human Maternal-Fetal Interface: Regulation and Functional Implications Am. J. Pathol., January 1, 2007; 170(1): 126 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bix, R. Castello, M. Burrows, J. J. Zoeller, M. Weech, R. A. Iozzo, C. Cardi, M. L. Thakur, C. A. Barker, K. Camphausen, et al. Endorepellin In Vivo: Targeting the Tumor Vasculature and Retarding Cancer Growth and Metabolism. J Natl Cancer Inst, November 15, 2006; 98(22): 1634 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Seidler, S. Goldoni, C. Agnew, C. Cardi, M. L. Thakur, R. T. Owens, D. J. McQuillan, and R. V. Iozzo Decorin Protein Core Inhibits in Vivo Cancer Growth and Metabolism by Hindering Epidermal Growth Factor Receptor Function and Triggering Apoptosis via Caspase-3 Activation J. Biol. Chem., September 8, 2006; 281(36): 26408 - 26418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Liu, M. Liao, J. G. Mielke, K. Ning, Y. Chen, L. Li, Y. H. El-Hayek, E. Gomez, R. S. Zukin, M. G. Fehlings, et al. Ischemic insults direct glutamate receptor subunit 2-lacking AMPA receptors to synaptic sites. J. Neurosci., May 17, 2006; 26(20): 5309 - 5319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Scott, C. M. Dodd, E. M. Bergmann, J. K. Sheehan, and P. N. Bishop Crystal Structure of the Biglycan Dimer and Evidence That Dimerization Is Essential for Folding and Stability of Class I Small Leucine-rich Repeat Proteoglycans J. Biol. Chem., May 12, 2006; 281(19): 13324 - 13332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mukherjee, M. Tessema, and A. Wandinger-Ness Vesicular Trafficking of Tyrosine Kinase Receptors and Associated Proteins in the Regulation of Signaling and Vascular Function Circ. Res., March 31, 2006; 98(6): 743 - 756. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |