Sustained Down-regulation of the Epidermal Growth Factor Receptor by Decorin

  • Csordás G
  • Santra M
  • Reed C
  • et al.
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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.

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Csordás, G., Santra, M., Reed, C. C., Eichstetter, I., McQuillan, D. J., Gross, D., … Iozzo, R. V. (2000). Sustained Down-regulation of the Epidermal Growth Factor Receptor by Decorin. Journal of Biological Chemistry, 275(42), 32879–32887. https://doi.org/10.1074/jbc.m005609200

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