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Int J Cancer. 2016 Jan 1;138(1):160-70. doi: 10.1002/ijc.29702. Epub 2015 Aug 10.

IKBB tumor suppressive role in nasopharyngeal carcinoma via NF-κB-mediated signalling.

Author information

  • 1Department of Clinical Oncology, University of Hong Kong, People's Republic of China.
  • 2Center for Cancer Research, University of Hong Kong, People's Republic of China.
  • 3Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, People's Republic of China.
  • 4Department of Pathology, HKU-Shenzhen Hospital, Shenzhen, People's Republic of China.
  • 5Department of Pathology, Tuen Mun Hospital, Hong Kong.
  • 6Department of Pathology, Princess Margaret Hospital, Hong Kong.
  • 7Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong.
  • 8Department of Oncology, Princess Margaret Hospital, Hong Kong.
  • 9Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong.

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.

© 2015 UICC.

KEYWORDS:

IKBB; NF-κB/Akt/GSK-3β signalling pathway; angiogenesis; tumor microenvironment; tumor suppressor

PMID:
26227166
[PubMed - indexed for MEDLINE]
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