MMPs*

Protein MMPs*

Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / MATRIX_REGULATION

References
PMID:16572188
Activated fibroblasts also secrete increased levels of ECM-degrading proteases such as matrix metalloproteinase 2 (MMP2), MMP3 and MMP9, facilitating increased ECM turnover and altered ECM composition.
MMPs probably allow cancer cells to cross tissue boundaries and escape the primary tumour site. MMPs and other proteases also directly affect the motility and invasiveness of cancer cells. Such a direct effect has been elucidated for MMP3 (also known as stromelysin 1), which is highly expressed in fibroblasts. MMP3 directly cleaves the extracellular domain of E-cadherin, prompting normal mammary epithelial cells to disaggregate and undergo EMT, promoting cancer-cell invasiveness88. MMP1 also shows such a tumour-promoting effect. The protease-activated receptor PAR1, which is a tethered-ligand receptor, is activated by proteolytic cleavage of the extracellular domain by MMP1, promoting cancer cell migration and invasion through PAR1-dependent Ca2+ signals.
PMID:20699369
activated fibroblasts through secretion of metalloproteinases elicit in cancer cells a clear epithelial-mesenchymal transition (EMT), as well as enhancement of tumor growth and development of spontaneous metastases.
exposure of HPFs to CM from PC3 cells or to IL-6 treatment, but not to TGF-?? treatment, elicits a strong increase in MMP-2 expression and the de novo appearance of MMP-9 (Fig. 3B). In addition, treatment of HPFs with IL-6???blocking antibodies during their exposure to CM from PC3 abrogates the upregulation of MMP expression (Fig. 3B). In keeping with our findings, we observed that the MMP inhibitor ilomastat reverts both the activation of the EMT process (Fig. 3C) and the proinvasive effect elicited by PCa-AFs on PC3 cells (Fig. 3D). In contrast, the EMT induction and the increase in PC3 invasiveness induced by MFs are insensitive to MMP inhibition
PMID:22809838
CAF-induced cetuximab resistance is dependent on the matrix metalloproteinases

Modifications:
In compartment: Cytosol

MMPs*@Cytosol

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