DECORIN SUPPRESSES TUMOR-CELL GROWTH BY ACTIVATING THE EPIDERMAL GROWTH-FACTOR RECEPTOR

Decorin, a small leucine-rich proteoglycan, is capable of suppressing the growth of various tumor cell lines when expressed ectopically. In this report, we investigated the biochemical mechanism by which decori n inhibits cell cycle progression. In A431 squamous carcinoma cells, d ecorin proteoglycan or protein core induced a marked growth suppressio n, when either exogenously added or endogenously produced by a transge ne. Decorin caused rapid phosphorylation of the EGF receptor and a con current activation of mitogen-activated protein (MAP) kinase signal pa thway. This led to a protracted induction of endogenous p21, a potent inhibitor of cyclin-dependent kinases, and ultimate cell cycle arrest. Biglycan, a related proteoglycan, had no effect. Moreover, decorin ac tivated the EGF receptor/MAP kinase/p21 axis in cell lines of various histogenetic backgrounds. These results provide the first evidence tha t EGF and decorin converge functionally to regulate the cell cycle thr ough activation of a common pathway which ultimately leads to growth s uppression.