Fucosyltransferase IV Enhances Expression of MMP-12 Stimulated by EGF via the ERK1/2, p38 and NF-kB Pathways in A431Cells

Yang, Xuesong; Liu, Shui-Ai; Liu, Jiwei; Qiu, Yan

doi:10.7314/apjcp.2012.13.4.1657

Cited by 22 publications

(15 citation statements)

References 39 publications

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“…To determine whether the ERK pathway is also involved in the inhibition of p65 phosphorylation by melatonin, we examined the ERK kinase pathway, as well as p38 and JNK activity. In fact, under the same conditions, the ERK pathway did not inhibit the release of activated NF-κB, a result that contrasts with data showing that the phosphorylation of ERK1/2 regulates the phosphorylation (and activation) of NF-κB [47]. Indeed, an ERK inhibitor attenuated the forcemediated stimulation of NF-κB DNA binding in human periodontal ligament fibroblasts but not in the presence of a JNK or p38 MAPK inhibitor [48].…”

Section: Melatonin Enhances the Effectiveness Of Cisplatin By Supprescontrasting

confidence: 53%

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

Liu

Fan

Chen

et al. 2015

Cell Physiol Biochem

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Background/Aims: Melatonin, synthesized by the pineal gland and released into the blood, appears to have antitumour properties; however, the mechanisms of its anti-cancer effects are largely unknown, especially in stomach cancer. Here, we explore the antitumour activity of melatonin in a gastric cancer cell line (AGS) and analyse its molecular mechanisms. Methods: AGS cells were treated with melatonin, and cell viability was assessed using a CCK-8 assay. Flow cytometry was performed to evaluate apoptosis, and protein expression was examined by Western blotting. Results: Melatonin significantly inhibited cell viability, clone formation, and cell migration and invasion and induced apoptosis in AGS cells. Moreover, MAPK pathways (p38, JNK and ERK) were activated by melatonin treatment, which also significantly increased caspase-3 cleavage and Bax protein expression and decreased Bcl-2 protein expression in a time-dependent manner. Our results demonstrate that p38 and JNK inhibitors (SB203580 and SP600125, respectively) prevented melatonin-induced apoptosis; thus, the propensity of p38 MAPK and JNK to promote apoptosis could be at least partly due to the inhibition of NF-κB p65 activation by p38 and JNK. Finally, melatonin was able to strengthen cisplatin-mediated antitumour effects in human gastric carcinoma cells by up-regulating the expression of Bax, down-regulating the expression of Bcl-2 and activating the caspase-dependent apoptotic pathway. Conclusion: Melatonin induced apoptosis in AGS cells by activating the caspase-dependent apoptotic pathway and by inhibiting the nuclear translocation of NF-κB p65, two processes that are regulated by p38 and JNK. Furthermore, melatonin significantly enhanced the anti-tumour effects of cisplatin, with low systemic toxicity. These new findings suggest that melatonin may act as a potent anti-tumour agent and may have great potential as an adjuvant therapy in the future.

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Section: Melatonin Enhances the Effectiveness Of Cisplatin By Supprescontrasting

confidence: 53%

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

Liu

Fan

Chen

et al. 2015

Cell Physiol Biochem

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“…Hence, our results are consistent with the notion that H2O2 plays a pivotal role in PKC activation via ROS generation. It has been shown that MAPK exists downstream of PKC and regulates many related transcription factors, including NF-κB and β-catenin, in several cell types, including human UCBMSCs and mouse ESCs (Yun et al, 2009;Yang et al, 2012;Lee do et al, 2013;Priyanka et al, 2013). We found that H2O2 was able to induce ERK and p38 MAPK activation, thereby stimulating NF-κB and β-catenin activation.…”

Section: Figurementioning

confidence: 52%

Reactive oxygen species induce MMP12‐dependent degradation of collagen 5 and fibronectin to promote the motility of human umbilical cord‐derived mesenchymal stem cells

Yun

Lee

et al. 2014

British J Pharmacology

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Background and PurposeReactive oxygen species (ROS) are potent regulators of stem cell behaviour; however, their physiological significance as regards MMP‐mediated regulation of the motility of human umbilical cord blood‐derived mesenchymal stem cells (UCB‐MSCs) has not been characterized. In the present study, we investigated the role of hydrogen peroxide (H2O2) and associated signalling pathways in promoting UCB‐MSCs motility.Experimental ApproachThe regulatory effects of H2O2 on the activation of PKC, MAPKs, NF‐κB and β‐catenin were determined. The expressions of MMP and extracellular matrix proteins were examined. Pharmacological inhibitors and gene‐specific siRNA were used to identify the signalling pathways of H2O2 that affect UCB‐MSCs motility. An experimental skin wound‐healing model was used to confirm the functional role of UCB‐MSCs treated with H2O2 in ICR mice.Key ResultsH2O2 increased the motility of UCB‐MSCs by activating PKCα via a calcium influx mechanism. H2O2 activated ERK and p38 MAPK, which are responsible for the distinct activation of transcription factors NF‐κB and β‐catenin. UCB‐MSCs expressed eight MMP genes, but only MMP12 expression was uniquely regulated by NF‐κB and β‐catenin activation. H2O2 increased the MMP12‐dependent degradation of collagen 5 (COL‐5) and fibronectin (FN) associated with UCB‐MSCs motility. Finally, topical transplantation of UCB‐MSCs treated with H2O2 enhanced skin wound healing in mice.Conclusions and ImplicationsH2O2 stimulated UCB‐MSCs motility by increasing MMP12‐dependent degradation of COL‐5 and FN through the activation of NF‐κB and glycogen synthase kinase‐3β/β‐catenin, which is critical for providing a suitable microenvironment for MSCs transplantation and re‐epithelialization of skin wounds in mice.

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“…24 We also found that FUT4 had a critical role in the MAPK pathway by mediating EGF-induced NF- κ B activation and increasing expression of MMP-12. 25 Given that FUT4 may have an important role in tumor metastasis, we were prompted in this study to explore its role in the induction of EMT in breast cancer cells. Based on our results, we propose that FUT4, via activation of NF- κ B and PI3K/Akt-GSK3 β signaling, enhances the expression of Snail, leading to acquisition of the mesenchymal phenotype in breast cancer cells.…”

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confidence: 99%

Role of fucosyltransferase IV in epithelial–mesenchymal transition in breast cancer cells

2013

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Epithelial–mesenchymal transition (EMT) is a crucial step in tumor progression and has an important role during cancer invasion and metastasis. Although fucosyltransferase IV (FUT4) has been implicated in the modulation of cell migration, invasion and cancer metastasis, its role during EMT is unclear. This study explores the molecular mechanisms of the involvement of FUT4 in EMT in breast cancer cells. Breast cancer cell lines display increased expression of FUT4, which is accompanied by enhanced appearance of the mesenchymal phenotype and which can be reversed by knockdown of endogenous FUT4. Moreover, FUT4 induced activation of phosphatidylinositol 3-kinase (PI3K)/Akt, and inactivation of GSK3β and nuclear translocation of NF-κB, resulting in increased Snail and MMP-9 expression and greater cell motility. Taken together, these findings indicate that FUT4 has a role in EMT through activation of the PI3K/Akt and NF-κB signaling systems, which induce the key mediators Snail and MMP-9 and facilitate the acquisition of a mesenchymal phenotype. Our findings support the possibility that FUT4 is a novel regulator of EMT in breast cancer cells and a promising target for cancer therapy.

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Fucosyltransferase IV Enhances Expression of MMP-12 Stimulated by EGF via the ERK1/2, p38 and NF-kB Pathways in A431Cells

Cited by 22 publications

References 39 publications

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

Melatonin Induces Cell Apoptosis in AGS Cells Through the Activation of JNK and P38 MAPK and the Suppression of Nuclear Factor-Kappa B: a Novel Therapeutic Implication for Gastric Cancer

Reactive oxygen species induce MMP12‐dependent degradation of collagen 5 and fibronectin to promote the motility of human umbilical cord‐derived mesenchymal stem cells

Role of fucosyltransferase IV in epithelial–mesenchymal transition in breast cancer cells

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