STAT3 activation induced by Epstein-Barr virus latent membrane protein1 causes vascular endothelial growth factor expression and cellular invasiveness via JAK3 And ERK signaling

Wang, Zhenlian; Feijun, Luo; Li, Lili; Yang, Lifang; Hu, Duosha; Ma, Xiaoqian; Lu, Zhongxin; Sun, Lun‐Quan; Cao, Yang

doi:10.1016/j.ejca.2010.07.008

Cited by 79 publications

(78 citation statements)

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“…pSTAT3 expression levels in CNE1-LMP1 cells were higher than in the HNE1 cells. One potential mechanism for this discrepancy may be that LMP1 could activate STAT3 phosphorylation through the MAPK/ ERK and JAK/STAT pathways [22] . Subsequently, the critical downstream proteins Survivin, Mcl-1, Bcl-2 and Cyclin D1, were down-regulated, ultimately leading to cell growth inhibition, cell cycle arrest and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…LMP1 plays an important role in the tumorigenesis and development of NPC and contributes to the promotion of invasion and metastasis [21] . Moreover, a recent study demonstrated that LMP1 could induce STAT3 phosphorylation through the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and Janus kinase (JAK)/STAT pathways [22] .…”

Section: Introductionmentioning

confidence: 99%

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Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation

Liu

Long

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate the mechanisms underlying the anticancer effect of celecoxib on nasopharyngeal carcinoma (NPC). Methods: NPC cell lines, HNE1 and CNE1-LMP1, were treated with various concentrations of celecoxib for 48 h. The antiproliferative effect of celecoxib was assessed using MTT assay. Both cell cycle profiles and apoptosis were analyzed using flow cytometry. Western blot was used to measure the levels of signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3 Y705 (pSTAT3 Y705 ), COX-2, Survivin, Mcl-1, Bcl-2 and Cyclin D1. Results: Celecoxib (10-75 µmol/L) inhibited the proliferation of the NPC cell lines in a dose-dependent manner. Celecoxib (25 and 50 µmol/L) induced apoptosis and cell-cycle arrest at the G 0 /G 1 checkpoint in the NPC cell lines, which was associated with significantly reduced STAT3 phosphorylation. The genes downstream of STAT3 (ie, Survivin, Mcl-1, Bcl-2 and Cyclin D1) were significantly down-regulated after exposure to celecoxib (25 and 50 µmol/L). Conclusion: The anticancer effects of celecoxib on NPC cell lines results from inducing apoptosis and cell cycle arrest, which may be partly mediated through the STAT3 pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation

Liu

Long

et al. 2012

Acta Pharmacol Sin

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“…It has been well known that LMP-1 can activate the Stat-3 signaling pathway [12,13]. In a previous study it has been documented that the expression of miR-204 was controlled by Stat-3 [9].…”

Section: The Lmp-1-mediated Stat-3 Pathway Is Involved In Mir-204 Dowmentioning

confidence: 99%

Down‐regulation of miRNA‐204 by LMP‐1 enhances CDC42 activity and facilitates invasion of EBV‐associated nasopharyngeal carcinoma cells

Deng

et al. 2014

FEBS Letters

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Edited by Angel NebredaKeywords: Nasopharyngeal carcinoma Epstein-Barr virus Latent membrane protein 1 miR-204 Cdc42 Stat-3 a b s t r a c t Nasopharayngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy. It is known that microRNAs are implicated in the progression of NPC. However, the role of miR-204 in NPC is poorly understood. In this study, we found that miR-204 was down-regulated in NPC cells and tissues. Low-level expression of miR-204 was significantly associated with a more aggressive and poor prognostic phenotype of NPC. We further found that EBV-encoded latent membrane protein 1 (LMP-1) suppressed miR-204 expression by activating Stat-3. Cdc42 was identified as a direct target of miR-204. Mir-204 inhibited EBV positive C666-1 cell invasion and metastasis partly through targeting cdc42.

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“…STAT3 activation leads to overexpression of genes involved in tumorigenesis and is constitutive in most primary human tumors (11)(12)(13). STAT3 plays a significant role in the pathogenesis of the γ-herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein-Barr virus (EBV), and herpesvirus saimiri (14)(15)(16), all of which exploit the oncogenic effects of phosphorylated STAT3 (pSTAT3).…”

mentioning

confidence: 99%

Signal transducer and activator of transcription 3 (STAT3) and survivin induction by varicella-zoster virus promote replication and skin pathogenesis

Sen¹,

Che²,

Rajamani³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Varicella-zoster virus (VZV) is a human α-herpesvirus that causes varicella (chickenpox) during primary infection and zoster (shingles) upon reactivation. Like other viruses, VZV must subvert the intrinsic antiviral defenses of differentiated human cells to produce progeny virions. Accordingly, VZV inhibits the activation of the cellular transcription factors IFN regulatory factor 3 (IRF3) and signal transducers and activators of transcription 1 (STAT1), thereby downregulating antiviral factors, including IFNs. Conversely, in this study, we found that VZV triggers STAT3 phosphorylation in cells infected in vitro and in human skin xenografts in SCID mice in vivo and that STAT3 activation induces the anti-apoptotic protein survivin. Small-molecule inhibitors of STAT3 phosphorylation and survivin restrict VZV replication in vitro, and VZV infection of skin xenografts in vivo is markedly impaired by the administration of the phospho-STAT3 inhibitor S3I-201. STAT3 and survivin are required for malignant transformation caused by γ-herpesviruses, such as Kaposi's sarcoma virus. We show that STAT3 activation is also critical for VZV, a nononcogenic herpesvirus, via a survivin-dependent mechanism. Furthermore, STAT3 activation is critical for the life cycle of the virus because VZV skin infection is necessary for viral transmission and persistence in the human population. Therefore, we conclude that takeover of this major cell-signaling pathway is necessary, independent of cell transformation, for herpesvirus pathogenesis and that STAT3 activation and up-regulation of survivin is a common mechanism important for the pathogenesis of lytic as well as tumorigenic herpesviruses.T he life cycle of varicella-zoster virus (VZV) in the human host depends on its tropism for T cells, skin, and neurons within sensory ganglia (1). As shown in the SCID mouse model of VZV pathogenesis, infected human T cells transport the virus to epidermal cells in human skin xenografts and to neural cells in dorsal root ganglia xenografts (2, 3). VZV establishes latency in sensory ganglia; upon reactivation, the virus migrates to the skin via axonal transport to cause zoster.VZV modulates several signaling pathways to replicate efficiently in vitro, and these regulatory effects are especially important in differentiated skin cells infected in vivo. VZV interferes with IFN induction and signaling via inhibition of IFN regulatory factor 3 (IRF3), NFκB, and STAT1 in vitro and in skin (4, 5). However, the pathogenesis of VZV skin infection requires a mechanism to overcome the constitutive IFNα expression by epidermal cells that accounts for the 10-to 21-d interval between VZV transfer into skin and the appearance of lesions at skin surfaces (6). How VZV overcomes this cutaneous IFN barrier and produces skin vesicles is not known.The STATs are ubiquitous transcription factors with many cellular functions and are at the junction of several cytokinesignaling pathways (7,8). Of the seven STAT family proteins, STAT3 exerts widespread effects through transcri...

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STAT3 activation induced by Epstein-Barr virus latent membrane protein1 causes vascular endothelial growth factor expression and cellular invasiveness via JAK3 And ERK signaling

Cited by 79 publications

References 50 publications

Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation

Celecoxib induces apoptosis and cell-cycle arrest in nasopharyngeal carcinoma cell lines via inhibition of STAT3 phosphorylation

Down‐regulation of miRNA‐204 by LMP‐1 enhances CDC42 activity and facilitates invasion of EBV‐associated nasopharyngeal carcinoma cells

Signal transducer and activator of transcription 3 (STAT3) and survivin induction by varicella-zoster virus promote replication and skin pathogenesis

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