Mechanistically, we found that the phosphatidylinositol 3-kinase-AKT signal pathway and its downstream effectors, such as tissue inhibitor of metalloproteinases 1 and matrix metallopeptidase 9, were required for MUC13-mediated tumor metastasis of iCCA.
Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a multifunctional natural matrixin inhibitor that is generally considered a negative regulator of cancer metastasis.
MMP and TIMP play an important role in the degradation of extracellular matrix components which are essential for tumor growth, invasion and metastasis.
Molecularly targeted anti-cancer drugs inhibit the invasion and metastasis of hepatocellular carcinoma by regulating the expression of MMP and TIMP gene families.
Increased expression of TIMP-1 was observed in PNF in early-stage disease with no metastasis, while marked expression of CDH-1 and Ki67 occurred in late-stage FMC.
We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both <i>in vitro</i> techniques and animal models.
Our findings reveal a novel regulation of Rab37 activity by PKCα-mediated phosphorylation which inhibits exocytic transport of TIMP1 and thereby enhances lung tumor metastasis.
These findings provide the first evidence that the imbalance of MMP-9/TIMP-1, is one of the regulation mechanisms by which ESM1 promotes tumorigenicity and metastasis of prostate cancer cells.
Suppressing MMP-9 activity through the overexpression of TIMP-1 allows for regulation of tumor growth and metastasis by blocking invasion and angiogenesis in the tumor microenvironment.
Aspirin treatment significantly resulted in reduction of matrix metalloproteinase-9 (MMP-9) and upregulation of tissue inhibitors of metalloproteinase-1 (TIMP-1) activity, which are the proteolytic enzymes contributing to the degradation of extracellular matrix and basement membrane in cell invasion and metastasis.
Docosahexaenoic acid could downregulate the expressions of WAVE3, vascular endothelial cell growth factor, and MMP-9, and upregulate KISS-1, TIMP-1, and PPAR-γ, which negatively correlated with cell invasion and metastasis (*P < 0.05).
Thus, these results provide novel evidence that p-cymene is an effective candidate for the prevention of tumor invasion and metastasis through mechanisms that include the inhibition of MMP-9 expression and the augmentation of TIMP-1 production along with the suppression of ERK1/2 and p38 MAPK signal pathways in tumor cells.
The tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits the extracellular matrix-degrading activity of several matrix metalloproteinases, thereby regulating cancer cell invasion and metastasis.
The CPT1A silenced cells showed an up-regulated transcription of pro-apoptotic genes (BAD, CASP9, COL18A1) and down-modulation of invasion and metastasis related-genes (TIMP-1, PDGF-A, SERPINB2).
In this study several metalloproteases such as MMP-1, MMP-3, MMP-9, and TIMP-1 together with molecules from the fibrinolytic system like uPA, its receptor uPAR, and its inhibitor, PAI-1, were studied by immune-histochemistry to establish a comparison with and without metastasis.
In summary, this study presents novel functions of TIMP-1 in promoting cancer metastasis and suggests TIMP-1 is a potential tissue biomarker for lymph invasion and distant metastasis of lung adenocarcinoma.
In this study, we found that TIMP-1 expression in HCC tissues is associated with advanced TNM stage, intrahepatic metastasis, portal vein invasion, and vasculature invasion.
Degradation of the extracellular matrix (ECM), a critical step in cancer metastasis, is determined by the balance between MMPs (matrix metalloproteinases) and their inhibitors TIMPs (tissue inhibitors of metalloproteinases).