MMP11

Official Full Name

matrix metallopeptidase 11

Organism

Homo sapiens

GeneID

4320

Background

Proteins of the matrix metalloproteinase (MMP) family are 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the enzyme encoded by this gene is activated intracellularly by furin within the constitutive secretory pathway. Also in contrast to other MMP's, this enzyme cleaves alpha 1-proteinase inhibitor but weakly degrades structural proteins of the extracellular matrix. [provided by RefSeq, Jul 2008]

Synonyms

ST3; SL-3; STMY3;

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Detailed Information

MMP-11 belongs to the MMPs family and has some unique characteristics. MMP-11 can degrade the non-extracellular matrix of serine protease inhibitor, α1 antitrypsin and insulin-like growth factor binding protein-1. Most MMPs are secreted outside the cell as inactive zymogens and are activated outside the cell. It has been clinically found that MMP-11 is expressed in most malignant tumors such as breast cancer, pancreatic cancer, oral cancer and esophageal cancer tissues.

MMP-11 Related Signaling Pathway

In some established cell lines (such as MCF-7), MMP-11 is overexpressed, which may be related to the activation of Akt and Erk1/2. Activated Akt regulates the expression of several cell invasion and metastasis-associated proteins by direct phosphorylation or regulation of upstream regulatory factor expression. The Erk/MAPK pathway regulates several different cellular movements, including the breakdown of focal adhesions and the activation of guanosine triphosphatase in the Rho family involved in cell invasion and metastasis. In addition, studies have found that overexpression of MMP-11 may be involved in the activation of an insulin-like growth factor 1 (IGF-1) release involved in tumor invasion and may be associated with the MAPK signaling pathway.

MMP11 Figure 1. The expression pattern of MMP-11 in cancer microenvironment.（ Zhang, X., et al. 2016）

MMP-11 and Tumor

The study found that the occurrence and development of malignant tumors in MMP-11 deficient mice changed significantly. MMP-11 deletion inhibits the ability of 7,12-dimethylbenzindole to induce tumorigenesis, and fibroblasts in MMP-11 deficient mice also lose the ability to promote local planting of MCF7 tumor cell lines. The mechanism of action of MMP-11 may be related to apoptosis, and is related to the SP1 site and the ERK1/2-mitogen activated protein kinase (MAPK) signaling pathway. The study found that MMP-11 can inhibit the apoptosis of cancer cells and promote tumor growth. The study found that the apoptosis and necrosis of tumor cells were significantly higher in MMP-11-deficient mice than in wild-type mice. This indicates that MMP-11 reduces tumor cell apoptosis and necrosis and affects tumor progression. Studies have found that MMP-11 creates an environment conducive to the survival of tumor cells by altering the matrix environment, affecting the progression of the tumor. The fat infiltration and apoptosis of tumor cells in MMP-11 deficient mice were significantly improved.

It was first discovered that MMP-11 is expressed in interstitial fibroblasts of advanced breast cancer patients. Clinically, if it is detected in breast carcinoma in situ, it suggests the possibility of developing invasive carcinoma, and suggests that it may be a new type of breast cancer markers. The expression of MMP-11 was not associated with tumor pathological type, age of the patient, progesterone receptor and human epidermal growth factor receptor 2 expression, but was associated with menopausal status and estrogen receptor. The study identified 9 cases of breast carcinoma in situ and invasive carcinoma by pairing and considered MMP-11 to be one of the genes involved in breast cancer invasion. These experimental results confirm that MMP-11 overexpression in tumor tumors is closely related to the occurrence and development of breast tumors. In the study of invasive laryngeal cancer and laryngeal dysplasia, tumorigenesis and development were consistent with the expression of MMP-11, while MMP-11 positive in laryngeal carcinoma had significant DNA aberrations compared with MMP-11 negative, so MMP -11 positive tumors should be highly malignant.

References:

Pavida, P. , Jitlada, M. , Ornicha, P. , Mayumi, K. , & Mamitaro, O. . (2016). Role of matrix metalloproteinases in photoaging and photocarcinogenesis. International Journal of Molecular Sciences, 17(6), 868.
Zhang, X. , Huang, S. , Guo, J. , Zhou, L. , You, L. , & Zhang, T. , et al. (2016). Insights into the distinct roles of mmp-11 in tumor biology and future therapeutics (review). International Journal of Oncology, 48(5).
Isik, A, et al. Metalloproteinases and their inhibitors in patients with inguinal hernia. World Journal of Surgery, 41(5), 1259-1266.

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