title: NF-κB p65 Subunit Is Modulated by Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) in Nasopharyngeal Carcinoma HONE1 and HK1 Cells.
abstract: NF-κB is a well-characterized transcription factor, widely known as a key player in tumor-derived inflammation and cancer development. Herein, we present the functional and molecular relevance of the canonical NF-κB p65 subunit in nasopharyngeal carcinoma (NPC). Loss- and gain-of-function approaches were utilized to reveal the functional characteristics of p65 in propagating tumor growth, tumor-associated angiogenesis, and epithelial-to-mesenchymal transition in NPC cells. Extracellular inflammatory stimuli are critical factors that trigger the NF-κB p65 signaling; hence, we investigated the components of the tumor microenvironment that might potentially influence the p65 signaling pathway. This led to the identification of an extracellular matrix (ECM) protein that was previously reported as a candidate tumor suppressor in NPC. Our studies on the Latent Transforming Growth Factor-β Binding Protein 2 (LTBP2) protein provides substantial evidence that it can modulate the p65 transcriptional activity. Re-expression of LTBP2 elicits tumor suppressive effects that parallel the inactivation of p65 in NPC cells. LTBP2 was able to reduce phosphorylation of p65 at Serine 536, inhibit nuclear localization of active phosphorylated p65, and impair the p65 DNA-binding ability. This results in a consequential down-regulation of p65-related gene expression. Therefore, the data suggest that the overall up-regulation of p65 expression and the loss of this candidate ECM tumor suppressor are milestone events contributing to NPC development.
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Kan
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China.
authors.forename: Wai Ho
authors.initials: WH
authors.lastname: Shuen
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Center for Cancer Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China.
authors.forename: Hong Lok
authors.initials: HL
authors.lastname: Lung
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Center for Cancer Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China.
authors.forename: Arthur Kwok Leung
authors.initials: AK
authors.lastname: Cheung
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Center for Cancer Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Center for Nasopharyngeal Carcinoma Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China.
authors.forename: Dora Lai-Wan
authors.initials: DL
authors.lastname: Kwong
authors.affiliation: Center for Nasopharyngeal Carcinoma Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong (SAR), PR China.
authors.forename: Wai Tong
authors.initials: WT
authors.lastname: Ng
authors.affiliation: Center for Nasopharyngeal Carcinoma Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Department of Clinical Oncology, The University of Hong Kong-Shen Zhen Hospital, PR China.
authors.forename: Anne Wing Mui
authors.initials: AW
authors.lastname: Lee
authors.affiliation: Center for Nasopharyngeal Carcinoma Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Department of Oncology, Princess Margaret Hospital, Hong Kong (SAR), PR China.
authors.forename: Chun Chung
authors.initials: CC
authors.lastname: Yau
authors.affiliation: Center for Nasopharyngeal Carcinoma Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong (SAR), PR China.
authors.forename: Roger Kai Cheong
authors.initials: RK
authors.lastname: Ngan
authors.affiliation: Center for Nasopharyngeal Carcinoma Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong (SAR), PR China.
authors.forename: Stewart Yuk
authors.initials: SY
authors.lastname: Tung
authors.affiliation: Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Center for Cancer Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China; Center for Nasopharyngeal Carcinoma Research, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong (SAR), PR China.
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
mesh_terms: D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: C509035:LTBP2 protein, human; D053779:Latent TGF-beta Binding Proteins; D016328:NF-kappa B; D051996:Transcription Factor RelA