p27KIP1 is involved in ERK1/2-mediated MMP-9 expression via the activation of NF-κB binding in the IL-7-induced migration and invasion of 5637 cells

Park, Sung Lyea; Lee, Eo-Jin; Kim, Wun-Jae; Moon, Sung‐Kwon

doi:10.3892/ijo.2014.2290

Cited by 30 publications

(28 citation statements)

References 27 publications

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“…We also examined the molecules downstream of IL-7R, such as CyclinD1, which is associated with cell proliferation [17], and MMP-9, which degrades the extracellular matrix and contributes to cell migration [18], in HBX-positive cells. Our data indicates that the expression of CyclinD1 and MMP-9 was increased in Huh-7-HBX and HepG2-HBX cells.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that the expression of IL-7R was increased in various tumors such as those of the lung, bladder, and breast [8, 18, 23]. Increased expression of IL-7R was also found to prevent apoptosis and promote proliferation and migration of tumor cells by activating intracellular pathways and upregulating the associated downstream molecules via binding to its ligand, IL-7.…”

Section: Discussionmentioning

confidence: 99%

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Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

Kong

Zhou

et al. 2016

J Exp Clin Cancer Res

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BackgroundInterleukin-7 receptor (IL-7R) is involved in the abnormal function of solid tumors, but the role and regulatory mechanisms of IL-7R in HBV-related hepatocellular carcinoma (HCC) are still unclear.MethodsGene and protein expression levels of IL-7R were examined in hepatoma cells transfected with hepatitis B virus (HBV) plasmids and in hepatoma cells transfected with the multifunctional nonstructural protein X (HBX). The expression of HBX and IL-7R was measured by immunohistochemical analysis in HBV-related HCC tissues. The role of NF-κB and Notch1 pathways in HBX-mediated expression of IL-7R in hepatoma cells was examined. Activation of IL-7R downstream of intracellular signaling proteins AKT, JNK, STAT5, and the associated molecules CyclinD1 and matrix metalloproteinase-9 (MMP)-9, was assessed in HBX-positive cells with or without treatment with IL-7R short hairpin RNA (shRNA). Additionally, the role of IL-7R in HBX-mediated proliferation and migration of hepatoma cells was investigated.ResultsThe expression of IL-7R was increased in hepatoma cells transfected with HBV plasmids; HBX was responsible for the HBV-mediated upregulation of IL-7R. Compared to adjacent tissues, the expression of HBX and IL-7R was increased in HBV-related HCC tissues. Additionally, the relative expression levels of HBX were associated with IL-7R in HBV-related HCC tissues. The activation of NF-κB pathways and expression of Notch1 were increased in hepatoma cells transfected with HBX, and inhibition of NF-κB and Notch1 pathways significantly decreased HBX-mediated expression of IL-7R. The activation of AKT and JNK and the expression of CyclinD1 and MMP-9 were increased in HBX-positive cells. When cells were treated with IL-7R shRNA, the activation of AKT and JNK, as well as the expression of CyclinD1 and MMP-9, were significantly inhibited. Additionally, IL-7R was responsible for HBX-induced proliferation and migration ability of hepatoma cells.ConclusionsOur data demonstrate that HBX can upregulate IL-7R via NF-κB and Notch1 pathways to facilitate the activation of intracellular pathways and expression of associated molecules, and contribute to proliferation and migration of hepatoma cells.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

Kong

Zhou

et al. 2016

J Exp Clin Cancer Res

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“…Curcumin was also observed to inhibit the invasion of EC cells at non-cytotoxic concentrations. MMP-2 and -9 play a significant role in the metastasis of tumor cells (14)(15)(16). By degrading the ECM, MMP-2 and -9 make the metastasis of tumor cells possible.…”

Section: Discussionmentioning

confidence: 99%

Curcumin suppresses migration and invasion of human endometrial carcinoma cells

et al. 2015

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Abstract. Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, following treatment with curcumin for 24 h, there was a decrease in the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in EC cells. Moreover, curcumin treatment significantly decreased the levels of the phosphorylated form of extracellular signalregulated kinase (ERK) 1/2. MEK1 overexpression partially blocked the anti-metastatic effects of curcumin. Combined treatment with ERK inhibitor U0126 and curcumin resulted in a synergistic reduction in MMP-2/-9 expression; the invasive capabilities of HEC-1B cells were also inhibited. In conclusion, curcumin inhibits tumor cell migration and invasion by reducing the expression and activity of MMP-2/9 via the suppression of the ERK signaling pathway, suggesting that curcumin is a potential therapeutic agent for EC.

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“…Ascorbic acid serves several functions in the CNS, including peptide amidation, myelin formation, synaptic potentiation and protection against glutamate toxicity [33]. NF-jB is a dimeric transcription factor activated by reactive oxygen species [2], and it has been shown that it up-regulates many inflammatory cytokines such as MMP-9 [34]. Vitamin C may neutralize free radicals and inhibit the NF-jB signalling pathway, thus reducing MMP-9 concentrations.…”

Section: Discussionmentioning

confidence: 99%

Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model

Allahtavakoli

Amin

Esmaeeli-Nadimi

et al. 2015

Basic Clin Pharmacol Toxicol

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Delayed treatment of stroke with recombinant tissue plasminogen activator (r-tPA) induces overexpression of matrix metalloproteinase 9 (MMP-9) which leads to breakdown of the blood-brain barrier (BBB) and causes more injuries to the brain parenchyma. In this study, the effect of ascorbic acid (AA), an antioxidant agent, on the delayed administration of r-tPA in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated. Forty male rats were randomly divided into four groups: untreated control rats (ischaemic animals), AA-treated (500 mg/kg; 5 hr after stroke) rats, r-tPA-treated (5 hr after stroke 1 mg/kg) rats and rats treated with the combination of AA and r-tPA. Middle cerebral artery occlusion was induced by occluding the right middle cerebral artery (MCA). Infarct size, BBB, brain oedema and the levels of MMP-9 were measured at the end of study. Neurological deficits were evaluated at 24 and 48 hr after stroke. Compared to the control or r-tPA-treated animals, AA alone (p < 0.001) or in combination with r-tPA (p < 0.05) significantly decreased infarct volume. Ascorbic acid alone or r-tPA + AA significantly reduced BBB permeability (p < 0.05), levels of MMP-9 (p < 0.05 versus control; p < 0.01 versus r-tPA) and brain oedema (p < 0.001) when compared to either the control or the r-tPA-treated animals. Latency to the removal of sticky labels from the forepaw was also significantly decreased after the administration of AA + r-tPA (p < 0.05) at 24 or 48 hr after stroke. Based on our data, acute treatment with AA may be considered as a useful candidate to reduce the side effects of delayed application of r-tPA in stroke therapy. Ischaemic brain injury (IBI) is one of the most common causes of mortality and morbidity in the world [1,2]. Ischaemic brain injury is accompanied by several side effects, including brain oedema, destruction of blood-brain barrier (BBB), inflammation and induction of oxidative stress [3]. Oxidative stress in turn leads to oedema and more destruction of BBB which causes additional brain damage [4]. Reperfusion with thrombolytic recombinant tissue plasminogen activator (r-tPA) remains the only treatment proved to be safe and effective when given within 3-4.5 hr after ischaemia onset [5]. It has been shown that delayed use of r-tPA leads to hyperperfusion which results in the accumulation of free radicals and the up-regulation of matrix metalloproteinases (MMPs) including 7] and these events lead to more injuries to the brain parenchyma. Under normal conditions, the endogenous and exogenous antioxidants scavenge free radicals and inhibit the harmful effects of oxidative stress [8]. Previous investigations revealed that after IBI, the concentrations of glutathione and ascorbic acid (AA) are decreased, while free radicals are increased [9,10], suggesting that increasing the concentration of AA, which may act as an antioxidant under these conditions, could be considered as new therapeutic strategy for treatment of IBI [11].One vitamer form of AA, vitamin C, is a...

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p27KIP1 is involved in ERK1/2-mediated MMP-9 expression via the activation of NF-κB binding in the IL-7-induced migration and invasion of 5637 cells

Cited by 30 publications

References 27 publications

Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

Hepatitis B virus X protein promotes interleukin-7 receptor expression via NF-κB and Notch1 pathway to facilitate proliferation and migration of hepatitis B virus-related hepatoma cells

Curcumin suppresses migration and invasion of human endometrial carcinoma cells

Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model

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