Abstract
The small leucine-rich proteoglycan decorin interacts with the epidermal growth factor receptor (EGFR) and triggers a signaling cascade that leads to elevation of endogenous p21 and growth suppression. We demonstrate that decorin causes a sustained down-regulation of the EGFR. Upon stable expression of decorin, the EGFR number is reduced by approximately 40%, without changes in EGFR expression. However, EGFR phosphorylation is nearly completely abolished. Concurrently, decorin attenuates the EGFR-mediated mobilization of intracellular calcium and blocks the growth of tumor xenografts by down-regulating the EGFR kinase in vivo. Thus, decorin acts as an autocrine and paracrine regulator of tumor growth and could be utilized as an effective anti-cancer agent.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphate / pharmacology
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Animals
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Calcium / metabolism
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Calcium Signaling / drug effects
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Calcium Signaling / physiology*
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Carcinoma, Squamous Cell / pathology*
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Carcinoma, Squamous Cell / therapy*
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Cell Division
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Decorin
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Down-Regulation / drug effects
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Down-Regulation / physiology*
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Epidermal Growth Factor / pharmacology
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ErbB Receptors / genetics*
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ErbB Receptors / metabolism
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Extracellular Matrix Proteins
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Female
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Humans
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Mice
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Mice, Nude
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Phosphorylation
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Proteoglycans / genetics
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Proteoglycans / pharmacology
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Proteoglycans / physiology*
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Recombinant Proteins / pharmacology
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Transfection
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Transforming Growth Factor beta / antagonists & inhibitors
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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DCN protein, human
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Dcn protein, mouse
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Decorin
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Extracellular Matrix Proteins
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Proteoglycans
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Recombinant Proteins
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Transforming Growth Factor beta
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Epidermal Growth Factor
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Adenosine Triphosphate
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ErbB Receptors
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Calcium