Role of The Epstein–Barr Virus-Encoded Latent Membrane Protein-1, LMP1, in The Pathogenesis of Nasopharyngeal Carcinoma

Morris, Mhairi A.; Dawson, Christopher W.; Young, Lawrence S.

doi:10.2217/fon.09.53

Cited by 88 publications

(79 citation statements)

References 110 publications

(54 reference statements)

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“…Latent membrane protein 1 (LMP1) is considered the major oncogene of EBV because it has transforming properties in cultured cell lines, is essential for B-lymphocyte transformation, and is frequently expressed in EBV-associated cancers (2,3). LMP1 functions as a constitutively active member of the tumor necrosis factor receptor family and activates multiple signaling pathways, including mitogen-activated protein kinase (MAPK), c-Jun Nterminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K)/Akt, and NF-κB (4). LMP1 induces the expression of specific genes that are involved with apoptosis, cell-cycle progression, cell proliferation, and migration (4).…”

mentioning

confidence: 99%

“…LMP1 functions as a constitutively active member of the tumor necrosis factor receptor family and activates multiple signaling pathways, including mitogen-activated protein kinase (MAPK), c-Jun Nterminal kinase (JNK), phosphatidylinositol 3-kinase (PI3K)/Akt, and NF-κB (4). LMP1 induces the expression of specific genes that are involved with apoptosis, cell-cycle progression, cell proliferation, and migration (4). One important target of LMP1 is epidermal growth factor receptor (EGFR), a member of the ErbB receptor tyrosine kinase family (5).…”

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confidence: 99%

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Human tumor virus utilizes exosomes for intercellular communication

Meckes

Shair

Marquitz

et al. 2010

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

473

498

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The Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) is expressed in multiple human malignancies and has potent effects on cell growth. It has been detected in exosomes and shown to inhibit immune function. Exosomes are small secreted cellular vesicles that contain proteins, mRNAs, and microRNAs (miRNAs). When produced by malignant cells, they can promote angiogenesis, cell proliferation, tumor-cell invasion, and immune evasion. In this study, exosomes released from nasopharyngeal carcinoma (NPC) cells harboring latent EBV were shown to contain LMP1, signal transduction molecules, and virus-encoded miRNAs. Exposure to these NPC exosomes activated the ERK and AKT signaling pathways in the recipient cells. Interestingly, NPC exosomes also contained viral miRNAs, several of which were enriched in comparison with their intracellular levels. LMP1 induces expression of the EGF receptor in an EBV-negative epithelial cell line, and exosomes produced by these cells also contain high levels of EGF receptor in exosomes. These findings suggest that the effects of EBV and LMP1 on cellular expression also modulate exosome content and properties. The exosomes may manipulate the tumor microenvironment to influence the growth of neighboring cells through the intercellular transfer of LMP1, signaling molecules, and viral miRNAs.

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confidence: 99%

mentioning

confidence: 99%

Human tumor virus utilizes exosomes for intercellular communication

Meckes

Shair

Marquitz

et al. 2010

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

473

498

View full text Add to dashboard Cite

show abstract

“…may involve the effects of LMP1 in regulating the mitogen-activated protein kinase (MAPK), NF-κB, and PI3K pathways [32]. Similarly, LMP2a, forms tyrosine-phosphorylated aggregates in the plasma membrane, associates with Lyn and Syk and stimulates B-cell receptor (BCR) signaling, thereby also inducing activation of the PI3K/AKT survival pathway [24,33].…”

Section: Mechanisms Of Oncogenesismentioning

confidence: 99%

Immunotherapy against cancer-related viruses

2016

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Approximately 12% of all cancers worldwide are associated with viral infections. To date, eight viruses have been shown to contribute to the development of human cancers, including Epstein-Barr virus (EBV), Hepatitis B and C viruses, and Human papilloma virus, among others. These DNA and RNA viruses produce oncogenic effects through distinct mechanisms. First, viruses may induce sustained disorders of host cell growth and survival through the genes they express, or may induce DNA damage response in host cells, which in turn increases host genome instability. Second, they may induce chronic inflammation and secondary tissue damage favoring the development of oncogenic processes in host cells. Viruses like HIV can create a more permissive environment for cancer development through immune inhibition, but we will focus on the previous two mechanisms in this review. Unlike traditional cancer therapies that cannot distinguish infected cells from non-infected cells, immunotherapies are uniquely equipped to target virus-associated malignancies. The targeting and functioning mechanisms associated with the immune response can be exploited to prevent viral infections by vaccination, and can also be used to treat infection before cancer establishment. Successes in using the immune system to eradicate established malignancy by selective recognition of virus-associated tumor cells are currently being reported. For example, numerous clinical trials of adoptive transfer of ex vivo generated virus-specific T cells have shown benefit even for established tumors in patients with EBV-associated malignancies. Additional studies in other virus-associated tumors have also been initiated and in this review we describe the current status of immunotherapy for virus-associated malignancies and discuss future prospects.

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“…20 Among these, calcium phosphate nanoparticles have emerged as a potential vector for nonviral gene delivery. [21][22][23] Hydroxyapatite [Ca 10 (OH) 2 (PO 4 ) 6, HA], a ceramic compound with a composition similar to that of mammalian bone and the dentin mineral compartment, has the advantages of absorbability and a high binding affinity with a variety of molecules, excellent biocompatibility, low cytotoxicity, nonimmunogenicity, lack of oncogenicity, and relatively high loading capacity and transfection efficiency. 24,25 Nanohydroxyapatite particles (nHAP) incorporating pEGFP-N1 are reportedly able to deliver DNA into gastric cancer cells without any significant cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%