IKBB tumor suppressive role in nasopharyngeal carcinoma via NF-κB-mediated signalling
Autor: | Yee Peng, Phoon, Arthur Kwok Leung, Cheung, Florence Man Fung, Cheung, Kui Fat, Chan, Shun, Wong, Bonnie Wing Yan, Wong, Stewart Yuk, Tung, Chun Chung, Yau, Wai Tong, Ng, Maria Li, Lung |
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Rok vydání: | 2015 |
Předmět: |
Adult
Male Glycogen Synthase Kinase 3 beta Nasopharyngeal Carcinoma Neovascularization Pathologic Tumor Suppressor Proteins Carcinoma NF-kappa B Down-Regulation Nasopharyngeal Neoplasms Middle Aged Prognosis Gene Expression Regulation Neoplastic Glycogen Synthase Kinase 3 Cell Movement Cell Line Tumor Cytokines Humans Female I-kappa B Proteins Proto-Oncogene Proteins c-akt Aged Neoplasm Staging Protein Binding Signal Transduction |
Zdroj: | International journal of cancer. 138(1) |
ISSN: | 1097-0215 |
Popis: | 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. |
Databáze: | OpenAIRE |
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