Epilysin (MMP-28)--structure, expression and potential functions

Abstract

Epilysin (MMP-28) is the newest member of the matrix metalloproteinase (MMP) family of extracellular proteases. Together the MMPs can degrade almost all components of the extracellular matrix (ECM). MMPs also regulate cell behaviour by releasing growth factors and biologically active peptides from the ECM by modulating cell surface receptors and adhesion molecules and by regulating the activity of mediators of the inflammatory pathways. Epilysin differs from most other MMPs as it is expressed in a number of normal tissues, suggestive of functions in tissue homeostasis. The epilysin homologue in Xenopus laevis (XMMP-28) is expressed in neural tissues, where it cleaves the neural cell adhesion molecule. Enhanced expression of epilysin has been observed in basal keratinocytes during wound healing and in different forms of cancer. There are, however, also reports on the downregulation of epilysin in malignant cells. The roles of epilysin in cancer seem to vary based on tumor type and stage of the disease. Importantly, epilysin can induce stable epithelial to mesenchymal transition (EMT) when overexpressed in epithelial lung carcinoma cells. Transforming growth factor beta (TGF-beta) is a crucial mediator of this process, which was characterized by the loss of E-cadherin and increased cell migration and invasion. Current results suggest a plausible interaction between epilysin and TGF-beta also under physiological circumstances, where epilysin activity may not induce EMT but, instead, trigger less permanent changes in TGF-beta signalling and cell motility.