scholarly journals Epstein–Barr virus LMP1 induces focal adhesions and epithelial cell migration through effects on integrin-α5 and N-cadherin

Oncogenesis ◽  
2015 ◽  
Vol 4 (10) ◽  
pp. e171-e171 ◽  
Author(s):  
L R Wasil ◽  
K H Y Shair
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Epstein Barr Virus ◽  
Focal Adhesions ◽  
Barr Virus ◽  
Epithelial Cell Migration ◽  
Integrin Α5 ◽  
Epstein Barr

scholarly journals Epstein-Barr-Virus-Encoded LMP2A Induces Primary Epithelial Cell Migration and Invasion: Possible Role in Nasopharyngeal Carcinoma Metastasis

2005 ◽  
Vol 79 (24) ◽  
pp. 15430-15442 ◽  
Author(s):  
Dirk M. Pegtel ◽  
Aravind Subramanian ◽  
Tzung-Shiahn Sheen ◽  
Ching-Hwa Tsai ◽  
Todd R. Golub ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Epstein Barr Virus ◽  
Cellular Migration ◽  
Migration And Invasion ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epithelial Cell Migration ◽  
Epstein Barr

ABSTRACT Nonkeratinizing nasopharyngeal carcinomas (NPC) are >95% associated with the expression of the Epstein-Barr virus (EBV) LMP2A latent protein. However, the role of EBV, in particular, LMP2A, in tumor progression is not well understood. Using Affymetrix chips and a pattern-matching computational technique (neighborhood analysis), we show that the level of LMP2A expression in NPC biopsy samples correlates with that of a cellular protein, integrin-alpha-6 (ITGα6), that is associated with cellular migration in vitro and metastasis in vivo. We have recently developed a primary epithelial model from tonsil tissue to study EBV infection in epithelial cells. Here we report that LMP2A expression in primary tonsil epithelial cells causes them to become migratory and invasive, that ITGα6 RNA levels are up-regulated in epithelial cells expressing LMP2, and that ITGα6 protein levels are increased in the migrating cells. Blocking antibodies against ITGα6 abrogated LMP2-induced invasion through Matrigel by primary epithelial cells. Our results provide a link between LMP2A expression, ITGα6 expression, epithelial cell migration, and NPC metastasis and suggest that EBV infection may contribute to the high incidence of metastasis in NPC progression.

Infection of Human Epithelial Cell Lines by Epstein-Barr Virus

ORL ◽  
1984 ◽  
Vol 46 (4) ◽  
pp. 195-201 ◽  
Author(s):  
Tom Takimoto ◽  
Kazuo Morishita ◽  
Ryozo Umeda ◽  
Hisashi Ogura ◽  
Motoichi Hatano
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Epstein Barr Virus ◽  
Human Epithelial Cell ◽  
Barr Virus ◽  
Epithelial Cell Lines ◽  
Epstein Barr

scholarly journals Hippo signaling effectors YAP and TAZ induce Epstein-Barr Virus (EBV) lytic reactivation through TEADs in epithelial cells

2021 ◽  
Vol 17 (8) ◽  
pp. e1009783
Author(s):  
Nicholas Van Sciver ◽  
Makoto Ohashi ◽  
Nicholas P. Pauly ◽  
Jillian A. Bristol ◽  
Scott E. Nelson ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Hippo Signaling ◽  
Oral Keratinocytes ◽  
Barr Virus ◽  
Ebv Infection ◽  
Lytic Reactivation ◽  
Epstein Barr

The Epstein-Barr virus (EBV) human herpesvirus is associated with B-cell and epithelial-cell malignancies, and both the latent and lytic forms of viral infection contribute to the development of EBV-associated tumors. Here we show that the Hippo signaling effectors, YAP and TAZ, promote lytic EBV reactivation in epithelial cells. The transcriptional co-activators YAP/TAZ (which are inhibited by Hippo signaling) interact with DNA-binding proteins, particularly TEADs, to induce transcription. We demonstrate that depletion of either YAP or TAZ inhibits the ability of phorbol ester (TPA) treatment, cellular differentiation or the EBV BRLF1 immediate-early (IE) protein to induce lytic EBV reactivation in oral keratinocytes, and show that over-expression of constitutively active forms of YAP and TAZ reactivate lytic EBV infection in conjunction with TEAD family members. Mechanistically, we find that YAP and TAZ interact with, and activate, the EBV BZLF1 immediate-early promoter. Furthermore, we demonstrate that YAP, TAZ, and TEAD family members are expressed at much higher levels in epithelial cell lines in comparison to B-cell lines, and find that EBV infection of oral keratinocytes increases the level of activated (dephosphorylated) YAP and TAZ. Finally, we have discovered that lysophosphatidic acid (LPA), a known YAP/TAZ activator that plays an important role in inflammation, induces EBV lytic reactivation in epithelial cells through a YAP/TAZ dependent mechanism. Together these results establish that YAP/TAZ are powerful inducers of the lytic form of EBV infection and suggest that the ability of EBV to enter latency in B cells at least partially reflects the extremely low levels of YAP/TAZ and TEADs in this cell type.

scholarly journals Tumorigenesis of Epstein–Barr Virus-Positive Epithelial Cell Lines Derived from Gastric Tissues in the SCID Mouse

Virology ◽  
2000 ◽  
Vol 277 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Masanao Murakami ◽  
Yoshiko Hoshikawa ◽  
Yukio Satoh ◽  
Hisao Ito ◽  
Masako Tajima ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cell Lines ◽  
Scid Mouse ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Epithelial Cell Lines ◽  
Epstein Barr

scholarly journals The Epstein-Barr Virus-Encoded EBNA1 Protein Activates the Bone Morphogenic Protein (BMP) Signalling Pathway to Promote Carcinoma Cell Migration

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 594 ◽  
Author(s):  
Hannah E. Bridgewater ◽  
Kathryn L. Date ◽  
John D. O’Neil ◽  
Chunfang Hu ◽  
John R. Arrand ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epstein Barr Virus ◽  
Carcinoma Cell ◽  
Bone Morphogenic Protein ◽  
Carcinoma Cells ◽  
Signalling Pathway ◽  
Barr Virus ◽  
Bmp Pathway ◽  
Epstein Barr ◽  
Bmp Signalling

The Epstein-Barr virus (EBV)-encoded nuclear antigen 1 (EBNA1) protein is expressed in all virus-associated malignancies, where it performs an essential role in the maintenance, replication and transcription of the EBV genome. In recent years, it has become apparent that EBNA1 can also influence cellular gene transcription. Here, we demonstrate that EBNA1 is able to stimulate the expression of the Transforming growth factor-beta (TGFβ) superfamily member, bone morphogenic protein 2 (BMP2), with consequential activation of the BMP signalling pathway in carcinoma cell lines. We show that BMP pathway activation is associated with an increase in the migratory capacity of carcinoma cells, an effect that can be ablated by the BMP antagonist, Noggin. Gene expression profiling of authentic EBV-positive nasopharyngeal carcinoma (NPC) tumours revealed the consistent presence of BMP ligands, established BMP pathway effectors and putative target genes, constituting a prominent BMP “signature” in this virus-associated cancer. Our findings show that EBNA1 is the major viral-encoded protein responsible for activating the BMP signalling pathway in carcinoma cells and supports a role for this pathway in promoting cell migration and possibly, metastatic spread.

scholarly journals Clustered MicroRNAs of the Epstein-Barr Virus Cooperatively Downregulate an Epithelial Cell-Specific Metastasis Suppressor

2014 ◽  
Vol 89 (5) ◽  
pp. 2684-2697 ◽  
Author(s):  
Teru Kanda ◽  
Mamiko Miyata ◽  
Makoto Kano ◽  
Satoru Kondo ◽  
Tomokazu Yoshizaki ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mirna Expression ◽  
Epstein Barr Virus ◽  
Epithelial Differentiation ◽  
Metastasis Suppressor ◽  
Barr Virus ◽  
Epstein Barr ◽  
Differentiation Marker ◽  
Bart Mirnas

ABSTRACTThe Epstein-Barr virus (EBV) encodes its own microRNAs (miRNAs); however, their biological roles remain elusive. The commonly used EBV B95-8 strain lacks a 12-kb genomic region, known as BamHI A rightward transcripts (BART) locus, where a number of BART miRNAs are encoded. Here, bacterial artificial chromosome (BAC) technology was used to generate an EBV B95-8 strain in which the 12-kb region was fully restored at its native locus [BART(+) virus]. Epithelial cells were stably infected with either the parental B95-8 virus or the BART(+) virus, and BART miRNA expression was successfully reconstituted in the BART(+) virus-infected cells. Microarray analyses of cellular gene expression identified N-myc downstream regulated gene 1 (NDRG1) as a putative target of BART miRNAs. The NDRG1 protein was barely expressed in B cells, highly expressed in epithelial cells, including primary epithelial cells, and strongly downregulated in the BART(+) virus-infected epithelial cells of various origins. Althoughin vitroreporter assays identified BART22 as being responsible for the NDRG1 downregulation, EBV genetic analyses revealed that BART22 was not solely responsible; rather, the entire BART miRNA cluster 2 was responsible for the downregulation. Immunohistochemical analyses revealed that the expression level of the NDRG1 protein was downregulated significantly in EBV-positive nasopharyngeal carcinoma specimens. Considering thatNDRG1encodes an epithelial differentiation marker and a suppressor of metastasis, these data implicate a causative relationship between BART miRNA expression and epithelial carcinogenesisin vivo.IMPORTANCEEBV-related epithelial cancers, such as nasopharyngeal carcinomas and EBV-positive gastric cancers, encompass more than 80% of EBV-related malignancies. Although it is known that they express high levels of virally encoded BART miRNAs, how these miRNAs contribute to EBV-mediated epithelial carcinogenesis remains unknown. Although a number of screenings have been performed to identify targets of viral miRNAs, many targets likely have not been identified, especially in case of epithelial cell infection. This is the first study to use EBV genetics to perform unbiased screens of cellular genes that are differentially expressed in viral miRNA-positive and -negative epithelial cells. The result indicates that multiple EBV-encoded miRNAs cooperatively downregulate NDRG1, an epithelial differentiation marker and suppressor of metastasis. The experimental system described in this study should be useful for further clarifying the mechanism of EBV-mediated epithelial carcinogenesis.

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