Role of epidermal growth factor receptor activation in regulating mucin synthesis

Abstract

Healthy individuals have few goblet cells in their airways, but in patients with hypersecretory diseases goblet-cell upregulation results in mucus hypersecretion, airway plugging, and death. Multiple stimuli produce hypersecretion via epidermal growth factor receptor (EGFR) expression and activation, causing goblet-cell metaplasia from Clara cells by a process of cell differentiation. These cells are also believed to be the cells of origin of non-small-cell lung cancer, but this occurs via cell multiplication. The mechanisms that determine which pathway is chosen are critical but largely unknown. Although no effective therapy exists for hypersecretion at present, the EGFR cascade suggests methods for effective therapeutic intervention.

Figure 1

The mechanism of EGFR expression and activation. Stimulation of airway epithelial cells with TNF-α causes EGFR expression (the extracellular and intracellular parts of EGFR are shown). EGFR ligands (produced by epithelial or nearby cells) bind to EGFR, resulting in EGFR tyrosine phosphorylation and a subsequent downstream cascade, which causes mucin gene and protein expression.