MMP14

Matrix metallopeptidase 11
Identifiers
Symbol	?
HGNC	7166
OMIM	185260
Other data
EC number	3.4.24.24

Matrix metallopeptidase 11 (MMP11), also known as stromelysin-3, is an enzyme that in humans is encoded by the MMP11 gene. MMP11 is a member of the matrix metalloproteinase (MMP) family, which is involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis.

Structure

MMP11 is synthesized as a zymogen, which is an inactive precursor that requires proteolytic cleavage for activation. Unlike most MMPs, MMP11 is activated intracellularly by furin, a proprotein convertase, before being secreted. The active enzyme consists of a catalytic domain with a zinc ion at its active site, which is characteristic of metalloproteinases.

Function

MMP11 is unique among MMPs in that it has a preference for cleaving non-matrix substrates, such as serine protease inhibitors (serpins), rather than extracellular matrix components. This suggests that MMP11 may play a role in modulating the tumor microenvironment and facilitating cancer cell invasion and metastasis. MMP11 is often overexpressed in breast cancer and other malignancies, and its expression is associated with poor prognosis.

Regulation

The expression of MMP11 is regulated at multiple levels, including transcriptional, post-transcriptional, and post-translational mechanisms. Transcription factors such as AP-1 and NF-κB can bind to the promoter region of the MMP11 gene and modulate its expression. Additionally, MMP11 activity can be inhibited by tissue inhibitors of metalloproteinases (TIMPs), although it is less sensitive to TIMP inhibition compared to other MMPs.

Clinical Significance

Due to its role in cancer progression, MMP11 is considered a potential target for therapeutic intervention. Inhibitors of MMP11 are being investigated for their ability to prevent tumor growth and metastasis. Furthermore, MMP11 expression levels can serve as a biomarker for cancer diagnosis and prognosis.

Research Directions

Current research is focused on understanding the precise biological functions of MMP11 in normal and pathological conditions, as well as developing specific inhibitors that can selectively target MMP11 without affecting other MMPs. Studies are also exploring the role of MMP11 in other diseases, such as fibrosis and cardiovascular disease.

Also see

• Matrix metalloproteinase
• Extracellular matrix
• Cancer metastasis
• Tissue inhibitor of metalloproteinases