title: IKBB tumor suppressive role in nasopharyngeal carcinoma via NF-κB-mediated signalling.
abstract: Tumor suppressor genes (TSGs) play a prominent role in cancer and are important in the development of nasopharyngeal carcinoma (NPC), which is endemic in Southern China as well as Southeast Asia. Apart from TSGs, aberrant signalling pathways are also commonly associated with tumor progression. Unsurprisingly, the NF-κB pathway is frequently associated with angiogenesis and promoting tumor growth and development. Functional complementation studies using microcell-mediated chromosome transfer helped to identify IKBB as a putative TSG in NPC. IKBB, an inhibitor of NF-κB, has recently been shown to be inversely associated with tumor growth and metastasis via inactivation of the NF-κB pathway, but its suppressive role is still only poorly understood. This study takes the lead in revealing the suppressive role of IKBB in NPC. IKBB is silenced in the majority of NPC tumor tissues in all stages. Its suppressive role is substantiated by perturbation in tumor formation, cell migration and angiogenesis. Interestingly, IKBB not only affects the 'seed', but also influences the 'soil' by downregulating the transcriptional level of proangiogenic factors Rantes, Upar, IL6, and IL8. For the first time, our data establish the importance of a novel tumor suppressive IKBB gene in abrogating angiogenesis in NPC via the NF-κB signalling pathway, which is likely mediated by crosstalk with the Akt/Gsk3β signalling pathway.
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, People's Republic of China.
authors.forename: Yee Peng
authors.initials: YP
authors.lastname: Phoon
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, People's Republic of China.|Center for Cancer Research, University of Hong Kong, People's Republic of China.
authors.forename: Arthur Kwok Leung
authors.initials: AK
authors.lastname: Cheung
authors.affiliation: Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, People's Republic of China.|Department of Pathology, HKU-Shenzhen Hospital, Shenzhen, People's Republic of China.
authors.forename: Florence Man Fung
authors.initials: FM
authors.lastname: Cheung
authors.affiliation: Department of Pathology, Tuen Mun Hospital, Hong Kong.
authors.forename: Kui Fat
authors.initials: KF
authors.lastname: Chan
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong.
authors.forename: Shun
authors.initials: S
authors.lastname: Wong
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, People's Republic of China.
authors.forename: Bonnie Wing Yan
authors.initials: BW
authors.lastname: Wong
authors.affiliation: Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, People's Republic of China.|Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong.
authors.forename: Stewart Yuk
authors.initials: SY
authors.lastname: Tung
authors.affiliation: Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, People's Republic of China.|Department of Oncology, Princess Margaret Hospital, Hong Kong.
authors.forename: Chun Chung
authors.initials: CC
authors.lastname: Yau
authors.affiliation: Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, People's Republic of China.|Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong.
authors.forename: Wai Tong
authors.initials: WT
authors.lastname: Ng
authors.affiliation: Department of Clinical Oncology, University of Hong Kong, People's Republic of China.|Center for Cancer Research, University of Hong Kong, People's Republic of China.|Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, People's Republic of China.
authors.forename: Maria Li
authors.initials: ML
authors.lastname: Lung
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics; D011379:Prognosis; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
keywords: IKBB; NF-κB/Akt/GSK-3β signalling pathway; angiogenesis; tumor microenvironment; tumor suppressor