Inhibition of constitutive NF‐κB activity suppresses tumorigenicity of ewing sarcoma EW7 cells

Javelaud, Delphine; Poupon, Marie‐France; Besançon, Françoise

doi:10.1002/ijc.10192

Cited by 24 publications

(10 citation statements)

References 34 publications

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“…A recent study has identified that the inhibitor of the NF-kBa/NF-kB signaling pathway was involved in the mRNA and protein expression of MMP-2 in human ciliary muscle cells (Lan et al, 2009). The downregulation of the inhibitor of NF-kBa or upregulation of phosphorylated NF-kB could induce NF-kB nuclear translocation and consequently promote the increase of MMPs in several types of human cells (Javelaud et al, 2002;Park et al, 2007;Zhao et al, 2013). Furthermore, NF-kB regulates the expression of u-PA and its receptor, and expression of both u-PA and the u-PA receptor correlates with invasive cancer cell phenotype and poor prognosis in highly invasive breast cancer cells (Sliva, 2004).…”

Section: Discussionmentioning

confidence: 99%

Berberine Reverses Epithelial-to-Mesenchymal Transition and Inhibits Metastasis and Tumor-Induced Angiogenesis in Human Cervical Cancer Cells

et al. 2014

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Metastasis is the most common cause of cancer-related death in patients, and epithelial-to-mesenchymal transition (EMT) is essential for cancer metastasis, which is a multistep complicated process that includes local invasion, intravasation, extravasation, and proliferation at distant sites. When cancer cells metastasize, angiogenesis is also required for metastatic dissemination, given that an increase in vascular density will allow easier access of tumor cells to circulation, and represents a rational target for therapeutic intervention. Berberine has several anti-inflammation and anticancer biologic effects. In this study, we provided molecular evidence that is associated with the antimetastatic effect of berberine by showing a nearly complete inhibition on invasion (P , 0.001) of highly metastatic SiHa cells via reduced transcriptional activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Berberine reversed transforming growth factor-b1-induced EMT and caused upregulation of epithelial markers such as E-cadherin and inhibited mesenchymal markers such as N-cadherin and snail-1. Selective snail-1 inhibition by snail-1-specific small interfering RNA also showed increased E-cadherin expression in SiHa cells. Berberine also reduced tumor-induced angiogenesis in vitro and in vivo. Importantly, an in vivo BALB/c nude mice xenograft model and tail vein injection model showed that berberine treatment reduced tumor growth and lung metastasis by oral gavage, respectively. Taken together, these findings suggested that berberine could reduce metastasis and angiogenesis of cervical cancer cells, thereby constituting an adjuvant treatment of metastasis control.

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Section: Discussionmentioning

confidence: 99%

Berberine Reverses Epithelial-to-Mesenchymal Transition and Inhibits Metastasis and Tumor-Induced Angiogenesis in Human Cervical Cancer Cells

et al. 2014

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“…cmyc has been identified as a potential EWS-ets target gene (40) and as promoting malignant progression of Ewing's sarcoma (41). Activation of nuclear factor-nB was found to contribute to resistance of Ewing's sarcoma cells to apoptosis (42). Coexpression of Sp1 with EWS-ets oncoprotein enhances activation of vascular endothelial growth factor, the expression of which was shown to be a negative predictor of survival in Ewing's sarcoma (43).…”

Section: Discussionmentioning

confidence: 99%

Nucleophosmin as a Candidate Prognostic Biomarker of Ewing's Sarcoma Revealed by Proteomics

Kikuta¹,

Tochigi²,

Shimoda³

et al. 2009

Clinical Cancer Research

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Purpose: We aimed to identify novel prognostic biomarkers for Ewing's sarcoma by investigating the global protein expression profile of Ewing's sarcoma patients. Experimental Design: We examined the proteomic profile of eight biopsy samples from Ewing's sarcoma patients using two-dimensional difference gel electrophoresis. Three patients were alive and continuously disease-free over 3 years after the initial diagnosis (good prognosis group) and five had died of the disease within 2 years of the initial diagnosis (poor prognosis group). Results: The protein expression profiles produced using two-dimensional difference gel electrophoresis consisted of 2,364 protein spots, among which we identified 66 protein spots whose intensity showed >2-fold difference between the two patient groups. Mass spectrometric protein identification showed that the 66 spots corresponded to 53 distinct gene products. Pathway analysis revealed that 31 of 53 proteins, including nucleophosmin, were significantly related to bone tissue neoplasms (P < 0.000001). The prognostic performance of nucleophosmin was evaluated immunohistochemically on an additional 34 Ewing's sarcoma cases. Univariate and multivariate analyses revealed that nucleophosmin expression significantly correlated with overall survival (P < 0.01).Conclusions: These results establish nucleophosmin as a candidate of independent prognostic marker for Ewing's sarcoma patients. Measuring nucleophosmin in biopsy samples before treatment may contribute to the effective management of Ewing's sarcoma.

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“…Activation of NF-κB promotes the development of OS (14), while inhibition of NF-κB activity suppresses the tumorigenicity of Ewing sarcoma EW7 cells (24). It has been reported that NF-κB-mediated transcriptional upregulation of TNFAIP2 by the Epstein-Barr virus oncoprotein, LMP1, promotes cell motility in NPC (20).…”

Section: Discussionmentioning

confidence: 99%

Knockdown of TNFAIP1 inhibits growth and induces apoptosis in osteosarcoma cells through inhibition of the nuclear factor-κB pathway

et al. 2014

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Abstract. Tumor necrosis factor-α-inducible protein-1 (TNFAIP1) plays a role in DNA synthesis, DNA repair, cell apoptosis and human diseases including cancer, and may be involved in tumor progression and metastases. However, little is known concerning the function of TNFAIP1 in human osteosarcoma (OS). The aim of the present study was to investigate the function and underlying mechanisms of TNFAIP1 in human OS. The expression of TNFAIP1 was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentiviral-mediated TNFAIP1 siRNA (siTNFAIP1) on cell proliferation, invasive potential and apoptosis by MTT and Transwell assays and flow cytometric analysis in OS (MG-63 and U-2 OS) cells. The results showed that the expression of TNFAIP1 protein was significantly increased in OS tissues compared with that in adjacent noncancerous tissues (ANCTs) (73.3 vs. 48.9%, P=0.018), and was correlated with the distant metastasis of the patients with OS (P=0.029). Knockdown of TNFAIP1 suppressed cell proliferation and invasion, and induced cell apoptosis in the OS cells together with the downregulation of p65 nuclear factor-κB (NF-κB), proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2) and upregulation of caspase-3. Collectively, our findings indicate that high expression of TNFAIP1 is associated with distant metastasis of OS, and knockdown of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in OS cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer.

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Inhibition of constitutive NF‐κB activity suppresses tumorigenicity of ewing sarcoma EW7 cells

Cited by 24 publications

References 34 publications

Berberine Reverses Epithelial-to-Mesenchymal Transition and Inhibits Metastasis and Tumor-Induced Angiogenesis in Human Cervical Cancer Cells

Berberine Reverses Epithelial-to-Mesenchymal Transition and Inhibits Metastasis and Tumor-Induced Angiogenesis in Human Cervical Cancer Cells

Nucleophosmin as a Candidate Prognostic Biomarker of Ewing's Sarcoma Revealed by Proteomics

Knockdown of TNFAIP1 inhibits growth and induces apoptosis in osteosarcoma cells through inhibition of the nuclear factor-κB pathway

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