title: Upregulation of special AT-rich-binding protein 1 by Epstein-Barr virus latent membrane protein 1 in human nasopharyngeal cells and nasopharyngeal cancer.
abstract: A global regulator of chromatin remodelling and gene expression, special AT-rich-binding protein 1 (SATB1) has been implicated in promotion of growth and metastasis of a number of cancers. Here, we demonstrate that the principal oncogene of Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1) upregulates SATB1 RNA and protein expression in human nasopharyngeal cell lines. Silencing of endogenously expressed SATB1 with specific short hairpin RNA decreases cell proliferation and resistance to apoptosis induced by growth factor withdrawal. Additionally, we provide evidence that LMP1-mediated expression of Survivin, a multifunctional protein involved in promoting cell growth and survival, is mediated at least in part by SATB1 in human nasopharyngeal cells. Finally, we show that SATB1 protein levels are elevated in tissue samples from patients with nasopharyngeal carcinoma (NPC), and are directly correlated with the expression of LMP1. Taken together, our results suggest that SATB1 functions as a pro-metastatic effector of LMP1 signalling in EBV-positive NPC.
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa, 920-8641, Japan.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Endo
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Shackelford
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa, 920-8641, Japan.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Aga
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa, 920-8641, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Pagano
mesh_terms: D002277:Carcinoma; D002460:Cell Line; D049109:Cell Proliferation; D005786:Gene Expression Regulation / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D009666:Nose / Q000166:cytology; D010614:Pharynx / Q000166:cytology; D034741:RNA, Small Interfering; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D036961:Matrix Attachment Region Binding Proteins; D034741:RNA, Small Interfering; C076189:SATB1 protein, human; D014763:Viral Matrix Proteins