Invasion of breast cancer cells into collagen matrix requires TGF-α and Cdc42 signaling

Invasion of MDA-MB-231 breast cancer cells into three-dimensional (3-D) type I-collagen matrices depends on TGF-α. We characterized the steps of invasion mediated by TGF-α. Cell migration, as observed by videomicroscopy, was effectively stimulated by collagen, suggesting that TGF-α may specifically participate in the invasion of a 3-D collagen matrix. We assessed the role of small GTPases of the Rho family in the invasion. Cdc42 was found to be necessary for invasion but dispensable for cell migration. These results suggest that TGF-α mediates invasion into 3-D collagen matrices by initiating the formation of protrusions into collagen, likely through activation of Cdc42.