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IKBB tumor suppressive role in nasopharyngeal carcinoma via NF‐κB–mediated signalling
Author(s) -
Phoon Yee Peng,
Cheung Arthur Kwok Leung,
Cheung Florence Man Fung,
Chan Kui Fat,
Wong Shun,
Wong Bonnie Wing Yan,
Tung Stewart Yuk,
Yau Chun Chung,
Ng Wai Tong,
Lung Maria Li
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29702
Subject(s) - nasopharyngeal carcinoma , nf κb , cancer research , signalling , signalling pathways , medicine , nfkb1 , signal transduction , biology , receptor , microbiology and biotechnology , transcription factor , genetics , gene , radiation therapy
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.