Abstract
Cell migration is critical for animal development and physiological as well as pathological responses. One important step during cell migration is the formation of lamellipodia at the leading edge of migrating cells. Here we report that the second messenger cAMP inhibits the migration of mouse embryonic fibroblast cells and mouse breast tumor cells. cAMP acts downstream of the small GTPase Rac and interferes with the formation of lamellipodia. Moreover, cAMP decreases the phosphorylation of the myosin light chain at the leading edge of cells and increases the phosphorylation of the vasodilator-stimulated phosphoprotein. Together with our previous report of a positive role of another second messenger, cGMP, in lamellipodium formation, our data indicate that cAMP and cGMP play opposite roles in modulating lamellipodium formation.
Highlights
Lamellipodium formation is an important step during cell migration [3, 4]
We found that cAMP inhibits the migration of mouse embryonic fibroblasts (MEFs) and 4T1 breast tumor cells by interfering with the formation of lamellipodia at the leading edge during cell migration
To investigate whether this inhibitory role of cAMP in cell migration is unique to MEF cells, we studied the effect of forskolin on the migration of highly invasive mouse
Summary
Lamellipodium formation is an important step during cell migration [3, 4]. The lamellipodium is a specialized subcellular structure at the front of a migrating cell. We found that cAMP inhibits the migration of MEFs and 4T1 breast tumor cells by interfering with the formation of lamellipodia at the leading edge during cell migration. D, dosage-dependent inhibition of serum-induced MEF cell migration by forskolin is shown.
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