Host–tumor interactions in nasopharyngeal carcinomas

Gourzonès, Claire; Barjon, Clément; Busson, P.

doi:10.1016/j.semcancer.2012.01.002

Cited by 86 publications

(96 citation statements)

References 127 publications

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“…24,25 Using western blot analysis, we sought to investigate whether various tumor-related factors (for example, hypoxia, serum deprivation, cytokine stimulation and LMP1 expression) could induce TNFAIP2 expression at the protein level. Among the tested factors, LMP1 triggered the most potent induction of TNFAIP2 expression in NPC-TW02 cells (B4.6-fold versus the empty vector control; Supplementary Figure 1a).…”

Section: Resultsmentioning

confidence: 99%

NF-κB-mediated transcriptional upregulation of TNFAIP2 by the Epstein–Barr virus oncoprotein, LMP1, promotes cell motility in nasopharyngeal carcinoma

Liu

Chao

et al. 2013

Oncogene

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Nasopharyngeal carcinoma (NPC), which is closely associated with Epstein-Barr virus (EBV), is a metastasis-prone epithelial cancer. We previously showed that tumor necrosis factor α-induced protein 2 (TNFAIP2) is highly expressed in NPC tumor tissues and is correlated with metastasis and poor survival in NPC patients. However, the underlying mechanism remains unclear. In this study, we demonstrate that the EBV oncoprotein, latent membrane protein 1 (LMP1), can transcriptionally induce TNFAIP2 expression via NF-κB. Quantitative RT-PCR and western blotting revealed that LMP1 induces TNFAIP2 expression through its C-terminal-activating region (CTAR2) domain, which is required for transduction of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling. Inhibition of NF-κB activation or depletion of p65 (a component of NF-κB) by RNA interference abolished the LMP1-induced expression of TNFAIP2, whereas ectopic expression of p65 was sufficient to induce TNFAIP2 expression. Luciferase reporter assays showed that LMP1 transcriptionally induces TNFAIP2 expression through a newly identified NF-κB-binding site within the TNFAIP2 promoter (-3,869 to -3,860 bp). Immunohistochemical analysis of NPC biopsy specimens further revealed a significant correlation between the protein levels of TNFAIP2 and activated p65 (R=0.689, P<0.001), indicating that our findings are clinically relevant. Immunofluorescence microscopy and co-immunoprecipitation assays showed that TNFAIP2 associates with actin and is involved in the formation of actin-based membrane protrusions. Furthermore, transwell migration assays demonstrated that TNFAIP2 contributes to LMP1-induced cell motility. Collectively, these findings provide novel insights into the regulation of TNFAIP2 and its role in promoting NPC tumor progression.

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Section: Resultsmentioning

confidence: 99%

NF-κB-mediated transcriptional upregulation of TNFAIP2 by the Epstein–Barr virus oncoprotein, LMP1, promotes cell motility in nasopharyngeal carcinoma

Liu

Chao

et al. 2013

Oncogene

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“…NPC is known to be associated with a lymphocyte-rich stroma, and it has been suggested that the disease may rely on interactions with these immune cells for growth and development signals (15). It has previously been reported that CD8…”

Section: Discussionmentioning

confidence: 99%

“…Another hallmark of undifferentiated NPC is a marked and substantial infiltration of immune cells into the tumor microenvironment (13,14). There is evidence that interactions between these stromal immune cells and tumor cells are important in NPC growth and proliferation (15), and tumor cells may coopt immune escape mechanisms evolved by EBV to evade immunosurveillance (16,17).…”

Section: Introductionmentioning

confidence: 99%

Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes

Zhang

MacIsaac

Zhou

et al. 2017

Molecular Cancer Research

138

115

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Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated cancer characterized by a poor prognosis and a high level of lymphocyte infiltrate. Genetic hallmarks of NPC are not completely known but include deletion of the p16 (CDKN2A) locus and mutations in NF-kB pathway components, with a relatively low total mutational load. To better understand the genetic landscape, an integrated genomic analysis was performed using a large clinical cohort of treatment-na€ ve NPC tumor specimens. This genomic analysis was generally concordant with previous studies; however, three subtypes of NPC were identified by differences in immune cell gene expression, prognosis, tumor cell morphology, and genetic characteristics. A gene expression signature of proliferation was poorly prognostic and associated with either higher mutation load or specific EBV gene expression patterns in a subtype-specific manner. Finally, higher levels of stromal tumor-infiltrating lymphocytes associated with good prognosis and lower expression of a WNT and TGFb pathway activation signature.

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“…This concept is likely to apply to nasopharyngeal carcinoma (NPC), characterized by the consistent expression of oncogenic viral proteins in a context of inflammation and immune escape (1). In its typical undifferentiated form, NPC is constantly associated with the Epstein-Barr virus, whose genome is contained in the nuclei of all malignant cells, but not in the surrounding tissue.…”

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confidence: 99%

“…In future research, one major challenge will be to identify the predominant mechanisms of immune suppression for each clinical and molecular subtype of NPC or even for a given patient, at each stage of his treatment and surveillance. NPC clearly is a heterogeneous disease, in terms of growth pattern (with either early metastases or predominantly local growth), in terms of malignant cell phenotypes (with more or less epithelio-mesenchymal transition) or in terms of immune "contexture" (variable relative abundance of various types of T-lymphocytes, macrophages, NK cells and dendritic cells) (1,6,8). Although currently there is no consensus on molecular subcategories, it is obvious that the NPC malignant phenotypes can be supported by different genetic and epigenetic alterations as well as different modes of virus-cell interactions, for example a high, low or very low level of LMP1 expression (Lo KW, 17 th International…”

mentioning

confidence: 99%