Mechanisms of human skin cell motility

The extracellular matrix (ECM) in contact with the cells and the soluble growth factors (GFs) binding to their cell surface receptors are the two main signals that directly regulate cell motility. Human keratinocytes and dermal fibroblasts are two primary cell types in skin that must undergo migration for skin wounds to heal. In this cell migration, ECMs play an "active" role by providing the cells with both focal adhesions and a migration-initiating signal, even in the absence of GFs. In contrast, GFs cannot initiate cell migration in the absence of a pro-migratory ECM. Rather, GFs play a "passive" role by enhancing the ECM-initiated motility and giving the moving cells directionality. Inside the cells, the initiation signal of the ECM and the optimization signals of the GFs are propagated by both overlapping and discrete signaling networks. However, activation of no single signaling pathway by itself is sufficient to replace the role of ECMs or GFs. This review focuses on our current understanding of both the individual and the combined functions of ECMs and GFs in the control of skin cell motility. An abbreviation of the terminologies used in this article is provided.