Matrix Metalloproteinase 9 (MMP-9)-dependent Processing of βig-h3 Protein Regulates Cell Migration, Invasion, and Adhesion

Kim, Yeon Hyang; Kwon, Hyung‐Joo; Kim, Doo-Sik

doi:10.1074/jbc.m112.357863

Cited by 60 publications

(49 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…43 MMP9 has previously been identified as a downstream target of Src/FAK signaling. 44 Consistent with this and with the critical role of MMP9 in invasion, teriflunomide may suppress TNBC invasion by blocking MMP9 expression. Several studies linked TNBC to some growth factor receptors, such as EGFR 45 and IGF1R, 46 which were considered as major oncogenic factors and attractive therapeutic targets in the management of TNBC patients.…”

Section: Discussionsupporting

confidence: 61%

Featured Article: Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells

Huang

Zhang²,

Zhi

et al. 2014

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is defined as a group of primary breast cancers lacking expression of estrogen, progesterone, and human epidermal growth factor receptor-2 (HER-2) receptors, characterized by higher relapse rate and lower survival compared with other subtypes. Due to lack of identified targets and molecular heterogeneity, conventional chemotherapy is the only available option for treatment of TNBC, but non-discordant positive therapeutic efficacy could not be achieved. Here, we demonstrated that these TNBC cells were sensitive to teriflunomide, which was a well-known immunomodulatory drug for treatment of relapsing multiple sclerosis (MS). Potent anti-cancer effects in TNBC in vitro, including proliferation inhibition, cell cycle delay, cell apoptosis, and suppression of cell motility and invasiveness, could be achieved with this agent. Of note, we showed that multiple signals involved in TNBC proliferation, survival, migratory, and invasive potential were under regulation by teriflunomide. Among them, we identified down-regulation of growth factor receptors to abolish growth maintenance, suppression of c-Myc, and cyclin D1 to contribute to its anti-proliferative effect, modulation of components of cell cycle to induce S-phase arrest, degradation of Bcl-xL, and up-regulation of BAX via activation of MAPK pathway to induce apoptosis, and inhibition of epithelial-mesenchymal transition (EMT) process, matrix metalloproteinase-9 (MMP9) expression, and inactivation of Src/FAK to reduce TNBC migration and invasion. The results identified teriflunomide may be of therapeutic benefit for the more aggressive and difficult-to-treat breast cancer subtype, indicating the use of teriflunomide for clinical trials for treatment of TNBC patients.

show abstract

Section: Discussionsupporting

confidence: 61%

Featured Article: Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells

Huang

Zhang²,

Zhi

et al. 2014

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…MMP-9 production and activity could be induced by LPS, which is a common potent activator of inflammatory responses [22,23,24,25]. In addition, MMP-9 was closely associated with cell migration [4,5]. In the current study, we verified that LPS not only induced the production of MMP-9 mRNA and protein expression, but also induced the potential activity of MMP-9, as well as cell migration.…”

Section: Discussionsupporting

confidence: 71%

“…Since MMPs, especially MMP-9, are required for cell migration [3,4], we assessed the migration of RAW264.7 cells. LPS at 25-200 ng/mL induced a significant increase in cell migration following 24-h incubation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…These activities require the migration of macrophages to lesion sites. Migration, an important characteristic of macrophages, is mediated by matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) [3,4,5]. It has been acknowledged that MMPs, a family of highly conserved zinc-dependent endopeptidases, can regulate aspects of inflammation and contribute to the development of many inflammatory diseases [6].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acetylcholine Inhibits LPS-Induced MMP-9 Production and Cell Migration via the a7 nAChR-JAK2/STAT3 Pathway in RAW264.7 Cells

Yang

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Excessive activation of matrix metalloproteinase 9 (MMP-9) has been found in several inflammatory diseases. Previous studies have shown that acetylcholine (ACh) reduced the levels of pro-inflammatory cytokines and decreased tissue damage. Therefore, this study was designed to explore the potential effects and mechanisms of ACh on MMP-9 production and cell migration in response to lipopolysaccharide (LPS) stimulation in RAW264.7 cells. Methods: MMP-9 expression and activity were induced by LPS in RAW264.7 cells, and examined by real-time PCR, western blotting and gelatin zymography, respectively. ELISA was used to determine the changes in MMP-9 secretion among the groups. Macrophage migration was evaluated using transwell migration assay. Knockdown of a7 nicotinic acetylcholine receptor (a7 nAChR) expression was performed using siRNA transfection. Results: Pre-treatment with ACh inhibited LPS-induced MMP-9 production and macrophage migration in RAW264.7 cells. These effects were abolished by the a7 nAChR antagonist methyllycaconitine (MLA) and a7 nAChR siRNA. The a7 nAChR agonist PNU282987 was found to have an effect similar to that of ACh. Moreover, ACh enhanced the expression of JAK2 and STAT3, and the JAK2 inhibitor AG490 and the STAT3 inhibitor static restored the effect of ACh. Meanwhile, ACh decreased the phosphorylation and nuclear translocation of NF-κB, and this effect was abrogated in the presence of MLA. In addition, the JAK2 and STAT3 inhibitor abolished the inhibitory effects of ACh on phosphorylation of NF-κB. Conclusions: Activation of a7 nAChR by ACh inhibited LPS-induced MMP-9 production and macrophage migration through the JAK2/STAT3 signaling pathway. These results provide novel insights into the anti-inflammatory effects and mechanisms of ACh.

show abstract

“…TGFβ-induced protein (TGFBI, aka βig-h3) is a 68 kDa RGD motif-containing protein that binds to type I, II and IV collagens. This protein is induced by TGFβ and acts to inhibit cell adhesion, cell-ECM interaction and cell migration [49;50]. Various mutations are associated with corneal dystrophy.…”

Section: Resultsmentioning

confidence: 99%

Interleukin-1-induced changes in the glioblastoma secretome suggest its role in tumor progression

Tarassishin

Weatherly

et al. 2014

Journal of Proteomics

View full text Add to dashboard Cite

The tumor microenvironment including glial cells and their inflammatory products regulates brain tumor development and progression. We have previously established that human glioma cells are exquisitely sensitive to IL-1 stimulation leading us to undertake a comparative analysis of the secretome of unstimulated and cytokine (IL-1)-stimulated glioblastoma cells. We performed label-free quantitative proteomic analysis and detected 190 proteins which included cytokines, chemokines, growth factors, proteases, cell adhesion molecules, extracellular matrix (ECM) and related proteins. Measuring area under the curve (AUC) of peptides for quantitation, the IL-1-induced secretome contained 13 upregulated and 5 downregulated extracellular proteins (p<0.05) compared to controls. Of these, IL-8, CCL2, TNC, Gal-1 and PTX3 were validated as upregulated and SERPINE1, STC2, CTGF and COL4A2 were validated as downregulated factors by immunochemical methods. A major representation of the ECM and related proteins in the glioblastoma secretome and their modulation by IL-1 suggested that IL-1 induces its effect in part by altering TGFβ expression, activity and signaling. These findings enhance our understanding of IL-1-induced modulation of glioma microenvironment, with implications for increased tumor invasion, migration and angiogenesis. They further provide novel targets for the glioblastoma intervention.

show abstract

Matrix Metalloproteinase 9 (MMP-9)-dependent Processing of βig-h3 Protein Regulates Cell Migration, Invasion, and Adhesion

Cited by 60 publications

References 48 publications

Featured Article: Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells

Featured Article: Teriflunomide, an immunomodulatory drug, exerts anticancer activity in triple negative breast cancer cells

Acetylcholine Inhibits LPS-Induced MMP-9 Production and Cell Migration via the a7 nAChR-JAK2/STAT3 Pathway in RAW264.7 Cells

Interleukin-1-induced changes in the glioblastoma secretome suggest its role in tumor progression

Contact Info

Product

Resources

About