Here, we establish ARP101 as a dual-function small-molecule inhibitor against MT1-MMP ECM hydrolysis and autophagy signal-transducing functions in a model of grade IV glioblastoma cells.
On the basis of this screening, we generated protein monomers and a heterodimer that contain monovalent and bivalent binding epitopes to MMP-14 and integrin α<sub>v</sub>β<sub>3</sub> Among these proteins, the bi-specific heterodimer, which bound strongly to both MMP-14 and integrin α<sub>v</sub>β<sub>3</sub>, exhibited superior ability to inhibit MMP-2 activation and displayed the highest inhibitory activity in cell-based models of a MMP-14-, MMP-2-, and integrin α<sub>v</sub>β<sub>3</sub>-dependent glioblastoma and of endothelial cell invasiveness and endothelial capillary tube formation.
We demonstrate for the first time that tumor suppressor Tip60 down-regulates cell adhesion and MT1-MMP expression and thereby invasion of glioblastoma cells by suppressing NF-κB pathway.
Confocal microscopy and fluorescence resonance energy transfer (FRET) analysis revealed that overexpressing a cytoplasmic-deleted MT1-MMP recombinant protein mutant prevented MTCBP-1 recruitment to the intracellular leaf of plasma membrane in U87 glioblastoma cells.
Our experimental data demonstrated that these two microRNAs inhibited the translation of mRNA of MT1-MMP and down-regulated its proteolytic enzyme activities via targeting 3'UTR of mRNA of MT1-MMP, further decreased activating proMMP2 into active MMP2 in fibrosarcoma HT1080, benign prostatic hyperplasia epithelial cell BPH-1 and glioblastoma U87GM.
Given that expression of membrane type-1 matrix metalloproteinase (MT1-MMP) has been found to regulate expression of the autophagy biomarker Bcl-2/adenovirus E1B 19kDa interacting protein 3 (BNIP3), we sought to investigate possible signaling interplay mechanisms between MT1-MMP and BNIP3 in Concanavalin-A (ConA) lectin-activated U87 glioblastoma cells.
Given that membrane type-1 matrix metalloproteinase (MT1-MMP), a plasma membrane-anchored matrix metalloproteinase, is a glycoprotein strongly expressed in radioresistant and chemoresistant glioblastoma that mediates pro-apoptotic signalling in brain cancer cells, we investigated whether MT1-MMP could also signal autophagy.
The contributions of membrane type-1 matrix metalloproteinase (MT1-MMP) and of the glucose-6-phosphate transporter (G6PT) in sphingosine-1-phosphate (S1P)-mediated Ca(2+) mobilization were assessed in glioblastoma cells.
Given evidence that the ER-embedded glucose-6-phosphate transporter (G6PT) regulates glioblastoma cell survival and that MT1-MMP is a key enzyme in the cancer cell invasive phenotype, we explored the molecular link between G6PT and MT1-MMP.
To study the roles of these molecules in the invasion of astrocytic tumors more fully, stable transfectants expressing the MT1-MMP gene were developed in a U251 human glioblastoma cell line.
We also propose that TIMP-2 acts as a negative regulator of MT1-MMP-dependent activities promoted by the action of CaM inhibitors in U-87 glioblastoma cells.
We investigated the effect of HGF/SF on matrix metalloproteinase-2 (MMP-2), membrane type 1 matrix metalloproteinase (MT1-MMP) and tissue inhibitors of metalloproteinases (TIMPs), expressions of c-Met/HGF receptor-positive human glioblastoma cells.
Immunohistochemically, MT1-MMP and MT2-MMP are localized to the neoplastic astrocytes in glioblastoma samples (17/17 cases and 12/17 cases, respectively), which are also positive for MMP-2.