Preferred Label : Inhibition of Matrix Metalloproteinases Pathway;
NCIt related terms : Inhibition of Matrix Metalloproteinases;
Alternative definition : BIOCARTA: Cellular transformation is accompanied by many cellular changes, including
uncontrolled proliferation, loss of the differentiated cell morphology, and invasion
of the extracellular matrix. Degradation of the extracellular matrix is a key component
of tumor cell invasion into surrounding tissues. Matrix metalloproteinases (MMPs)
are a class of proteases secreted by tumor cells, degrading the proteins of the extracellular
matrix and allowing metastasis. Drug inhibitors of MMPs are one strategy to control
cancer and block metastasis. In searching for genes that reverse the rounded morphology
of transformed cells in culture, RECK was identified (reversion-inducing, cysteine-rich
protein with Kazal motifs). RECK is a membrane-anchored inhibitor of matrix metalloproteinases,
inhibiting MMP-2, MMP-9, and MT1-MMP. The processing of MMPs to their active form
occurs at the plasma membrane, making the localization of RECK at the membrane a key
to its potent activity as an inhibitor of MMP activity. Soluble secreted MMP inhibitors
have also been identified, TIMPs, which appear to be less active at inhibiting MMPs
and even perhaps to be essential for MMP maturation. The inhibition of MMPs by RECK
inhibits invasion of tissues, metastasis, and tumor angiogenesis, and is essential
for normal development. In addition to playing a role in tissue invasion in cancer,
the activity of MMPs in angiogenesis, inflammation, and development is regulated by
inhibitors such as RECK and TIMPs. RECK expression is inhibited by ras, suggesting
one component by which ras induces transformation. High levels of RECK expression
in tumors is correlated with cancer patient survival and overexpression of RECK may
offer a therapeutic strategy for the control of cancer. (This definition may be outdated
- see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_reckPathway;
Origin ID : C39219;
UMLS CUI : C1512776;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
