Effects of Tissue Factor, PAR-2 and MMP-9 Expression on Human Breast Cancer Cell Line MCF-7 Invasion

Lin, Zeng-Mao; Zhao, Jianxin; Duan, Xuening; Zhang, Lan-Bo; Ye, Jingming; Xu, Ling; Liu, Yinhua

doi:10.7314/apjcp.2014.15.2.643

Cited by 8 publications

(7 citation statements)

References 18 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on their unique ability to degrade gelatinases, a major constituent of the basement membrane, MMP-2 and MMP-9, are the most important MMPs involved in tumor invasion and metastasis (38). It has been reported that the expression levels and activities of MMPs are associated with an advanced stage of breast cancer, increased invasion of tumor cells and building of metastatic formations (39). Atorvastatin, a member of the statin drug family, suppresses the expression levels of MMP-2 and MMP-9 in human endothelial cells (40).…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells

Shen

Yuan²,

et al. 2012

Molecular Medicine Reports

View full text Add to dashboard Cite

Abstract. Breast carcinoma is the leading cause of cancer-associated mortality in female individuals worldwide. Previous studies have investigated the pro-apoptotic and antimetastatic effects of statins, and have demonstrated that simvastatin exhibits antitumor activity and potent chemopreventive effects. However, the mechanism underlying the effects of simvastatin in breast cancer remains to be elucidated. The present study demonstrated that simvastatin inhibited the proliferation of MDA-MB-231 human breast cancer cells in a dose-dependent manner, decreased the protein expression of B cell lymphoma 2 (Bcl-2) and increased the protein expression of Bcl-2-associated X protein in timeand dose-dependent manners. In addition, simvastatin arrested cells in the G 0 /G 1 phase of the cell cycle, downregulated the protein expression levels of cyclin D1 and cyclin-dependent kinase (CDK)2, mediated the mitochondria-dependent caspase cascade by increasing the protein expression levels of caspase-3, -8 and -9, and downregulated the protein expression of X-linked inhibitor of apoptosis, which induced cell apoptosis. In addition, simvastatin decreased the protein expression of matrix metalloproteinase (MMP)-2 and suppressed the activation of nuclear factor (NF)-κB in the MDA-MB-231 cells. Taken together, these results demonstrated that the antitumor effect of simvastatin in the human MDA-MB-231 breast cancer cell line was via the inhibition of cell proliferation, affecting the cell cycle, downregulating the expression levels of cyclin D1 and CDKs, inducing apoptosis and decreasing the expression of MMP-2, possibly by inhibiting the activation of NF-κB. Statin treatment may provide a novel therapeutic approach for the treatment of breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells

Shen

Yuan²,

et al. 2012

Molecular Medicine Reports

View full text Add to dashboard Cite

show abstract

“…The efficacy of TF/VIIa/PAR-2-mediated activation of angiogenic mediators is greater than that induced by PAR-1 signaling [ 38 ]. TF-triggered PAR-2 signaling also results in increased MMP-9 expression, which positively correlates with the invasiveness of MCF-7 breast tumor cells [ 70 ] and may be linked to MMP-9 response to arachidonic acid metabolism [ 117 ]. It was reported that TF/FVIIa/PAR-2 interactions are critical for MDA-MB-231 breast cancer cell migration and invasion toward NIH-3T3 fibroblast-conditioned medium [ 68 ].…”

Section: Pars and Proteases—cooperation In Cancer Progressionmentioning

confidence: 99%

Protease-activated receptors (PARs)—biology and role in cancer invasion and metastasis

Wojtukiewicz

Hempel

Sierko

et al. 2015

Cancer Metastasis Rev

112

120

View full text Add to dashboard Cite

Although many studies have demonstrated that components of the hemostatic system may be involved in signaling leading to cancer progression, the potential mechanisms by which they contribute to cancer dissemination are not yet precisely understood. Among known coagulant factors, tissue factor (TF) and thrombin play a pivotal role in cancer invasion. They may be generated in the tumor microenvironment independently of blood coagulation and can induce cell signaling through activation of protease-activated receptors (PARs). PARs are transmembrane G-protein-coupled receptors (GPCRs) that are activated by a unique proteolytic mechanism. They play important roles in vascular physiology, neural tube closure, hemostasis, and inflammation. All of these agents (TF, thrombin, PARs—mainly PAR-1 and PAR-2) are thought to promote cancer invasion and metastasis at least in part by facilitating tumor cell migration, angiogenesis, and interactions with host vascular cells, including platelets, fibroblasts, and endothelial cells lining blood vessels. Here, we discuss the role of PARs and their activators in cancer progression, focusing on TF- and thrombin-mediated actions. Therapeutic options tailored specifically to inhibit PAR-induced signaling in cancer patients are presented as well.

show abstract

“…A zinc-dependent proteinase family, the matrix metalloproteinases (MMPs), are believed to participate in numerous pathological processes due to their activity in extracellular matrix (ECM) degradation (4). MMPs are associated with non-neoplastic diseases including ischemia (5), trauma (6), and neoplastic diseases including glioma (7), and breast (8) and liver cancer (9). It is currently generally accepted that cancer cells invade through tissue by secreting these enzymes.…”

Section: Introductionmentioning

confidence: 99%

Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway

et al. 2015

View full text Add to dashboard Cite

Invasion and metastasis are the major causes of tumor-related mortality in lung cancer. It is believed that curcumin is an effective drug possessing anti-invasive and anti-metastatic activities in the treatment of cancer. However, the specific mechanisms remain unclear. In the present study, we investigated whether the PKCα/Nox-2/ATF-2/MMP-9 signaling pathway is involved in the invasive behavior of lung cancer and whether curcumin could inhibit invasion by modulating this pathway. The cytotoxic effect of curcumin was evaluated by MTT assay and the capacity of invasion was assessed by Transwell assay. siRNA and plasmid transfection techniques were used to study the function of targeted genes. Real-time PCR and western blot analysis were used to evaluate the expression levels of PKCα, Nox-2, MMP-9 and the phosphorylation of ATF-2. The results showed that curcumin inhibited the proliferation and invasion of A549 cells in a dose-dependent manner. Overexpression of MMP-9 enhanced the invasion of A549 cells. However, inhibition of MMP-9 by siRNA or curcumin suppressed cell invasion. Moreover, we also demonstrated the catalytic role of PKCα in expression of MMP-9 and cellular invasion in A549 cells, which was dependent on the expression of Nox-2 and phosphorylation of ATF-2. Finally, we also showed that curcumin dose-dependently reduced the expression of PKCα, P47phox, Nox-2 and phosphorylated ATF-2, as well as intracellular ROS generation, suggesting the inhibitory effect of curcumin on the activation of the PKCα/Nox-2/ROS/ATF-2 pathway. In conclusion, the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway is activated in lung cancer A549 cells, which could be modulated by curcumin to inhibit cell invasiveness.

show abstract

Effects of Tissue Factor, PAR-2 and MMP-9 Expression on Human Breast Cancer Cell Line MCF-7 Invasion

Cited by 8 publications

References 18 publications

Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells

Molecular mechanism underlying the anticancer effect of simvastatin on MDA-MB-231 human breast cancer cells

Protease-activated receptors (PARs)—biology and role in cancer invasion and metastasis

Curcumin inhibits the invasion of lung cancer cells by modulating the PKCα/Nox-2/ROS/ATF-2/MMP-9 signaling pathway

Contact Info

Product

Resources

About