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MMP14
Protein-coding gene in the species Homo sapiens From Wikipedia, the free encyclopedia
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Matrix metalloproteinase-14 is an enzyme that in humans is encoded by the MMP14 gene.[5]
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Structure
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Perspective
Matrix metalloproteinase-14 (MMP14), also known as MT1-MMP, is a zinc-dependent type I transmembrane metalloproteinase characterized by a modular structure that enables its diverse biological functions. The protein comprises an extracellular catalytic domain responsible for matrix degradation, a short 20-amino acid cytoplasmic tail, and a single transmembrane domain anchoring it to the cell membrane.[6][7] The gene encoding MMP14 is organized into ten exons, with the novel C-terminal peptide domains and the 3'-untranslated region encoded by a single large exon; this structure is distinct from other MMP family members.[8] The exons for the catalytic and pro-domains are unique to MMP14, while the hemopexin-like domains share similarity with other MMPs.[8] The short intracellular domain (ICD) of MMP14 contains a unique lysine residue (Lys581) that can be mono-ubiquitinated, a modification that regulates the enzyme’s trafficking and cellular invasion functions.[7] This structural arrangement allows MMP14 to localize its proteolytic activity to the pericellular environment, facilitating processes such as extracellular matrix remodeling, cell migration, and activation of other MMPs, notably pro-MMP2.[6][7]
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Function
MMP14 (matrix metalloproteinase-14) is a membrane-anchored enzyme with critical roles in tissue remodeling, development, and cellular metabolism.[9] Its primary function is the proteolytic degradation of extracellular matrix (ECM) components, which is essential for processes such as organ development, cell migration, and branching morphogenesis. MMP14 directly activates other MMPs, most notably MMP2, and indirectly activates MMP13 and MMP9, thereby amplifying ECM remodeling and facilitating cellular invasion, a mechanism particularly relevant in cancer metastasis. Beyond its catalytic activity, MMP14 interacts with cell surface molecules (such as CD44 and integrins) to modulate cell signaling and behavior. Studies in knockout mice have shown that loss of MMP14 leads to severe defects in collagen turnover, impaired adipogenesis, metabolic imbalance, and increased autophagy, highlighting its role in maintaining metabolic homeostasis and energy storage. MMP14 integrates extracellular matrix remodeling with intracellular energy regulation, making it an important regulator of both tissue structure and metabolic balance.[9]
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Clinical significance
Increased expression of MMP14 has been observed in several cancers, including bladder, breast, colorectal, and renal cancers, and is often associated with more advanced disease and poorer short-term prognosis.[10][11][12][13][14] High MMP14 expression in tumor tissues correlates with increased tumor progression, metastasis, and reduced survival rates, particularly in muscle-invasive bladder cancer and colorectal cancer.[12][13][14] In addition, MMP14 is involved in the tumor microenvironment, including its expression by cancer-associated fibroblasts, which may contribute to tumor recurrence and resistance to certain chemotherapies.[14] While these associations suggest that MMP14 could serve as a useful prognostic biomarker and potential therapeutic target, its precise role and clinical utility may vary depending on cancer type and context.[10][14]
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Further reading
External links
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