title: SYK interaction with ITGβ4 suppressed by Epstein-Barr virus LMP2A modulates migration and invasion of nasopharyngeal carcinoma cells.
abstract: Epstein-Barr virus (EBV)-encoded Latent Membrane Protein 2A (LMP2A) is an EBV latency-associated protein regularly expressed in nasopharyngeal carcinoma (NPC). In B cells, LMP2A activity resembles that of a constitutively activated antigen receptor, which recruits the Syk tyrosine kinase to activate a set of downstream signaling pathways. LMP2A also downregulates cellular Syk levels. In the present study, we demonstrate that Syk interacts with the integrin β4 subunit (ITGβ4) of integrin α6β4 in epithelial cells and that concurrent LMP2A expression interferes with this interaction by competitive binding to Syk. We find that both Syk and LMP2A have an effect on ITGβ4 cell surface expression. However, in LMP2A expressing cells, ITGβ4 remains concentrated at the cellular protrusions, an expression pattern characteristic of motile cells, including NPC-derived epithelial cells. This effect of LMP2A on ITGβ4 localization is associated with a greater propensity for migration and invasion in-vitro, and may contribute to the invasive property of LMP2A-expressing NPC.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.|Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Matskova
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: L-S Z
authors.initials: LS
authors.lastname: Rathje
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.|Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Gish
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Werner
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Ignatyev
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: N
authors.initials: N
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: F
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: B
authors.initials: B
authors.lastname: Hou
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Pawson
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.
authors.forename: I
authors.initials: I
authors.lastname: Ernberg
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D039663:Integrin beta4 / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D000072377:Syk Kinase; D014763:Viral Matrix Proteins / Q000502:physiology*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; C059834:ITGB4 protein, human; D039663:Integrin beta4; D047908:Intracellular Signaling Peptides and Proteins; D014763:Viral Matrix Proteins; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase