MMP17

MMP-17, also known as MT4-MMP, is a member of the matrix metalloproteinase (MMP) family. It is categorized as a membrane-type MMP (MT-MMP) and is anchored to the cell surface by a glycosylphosphatidylinositol (GPI) anchor rather than a transmembrane segment.

Gene and expression: The MMP17 gene encodes the MMP-17 protease. Expression is detected in several tissues, including epithelial and stromal compartments, and can be modulated during development, inflammation, and tumor progression.

Function: Like other MMPs, MMP-17 is a zinc-dependent endopeptidase that participates in pericellular proteolysis and extracellular matrix remodeling. Its membrane localization enables focused proteolysis at the cell surface and it can participate in the activation or processing of other proteases in the pericellular environment, contributing to cell migration, angiogenesis, and tissue remodeling.

Regulation: MMP-17 activity is controlled at multiple levels, including zymogen activation, expression levels, and inhibition by tissue inhibitors of metalloproteinases (TIMPs). Its GPI anchoring influences localization and interaction with substrates.

Clinical relevance: Altered expression or activity of MMP-17 has been observed in certain cancers and inflammatory conditions, and it has been investigated as a potential therapeutic target for limiting tumor invasion and metastasis. However, therapeutic development remains challenging due to functional redundancy among MMPs and safety considerations.

Structure: The protease contains the canonical zinc-binding catalytic motif of metalloproteinases and is anchored to the cell surface via a GPI linkage.