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Published on: February 28, 2019
IKBB tumor suppressive role in nasopharyngeal carcinoma via NF-κB-mediated signalling
Yee Peng Phoon1, Arthur Kwok Leung Cheung1,2, Florence Man Fung Cheung3,4
1Department of Clinical Oncology, University of Hong Kong, People's Republic of China.
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.
Insights
The IKBB gene acts as a tumor suppressor in nasopharyngeal carcinoma (NPC), inhibiting angiogenesis and tumor growth. Silencing of IKBB is common in NPC, highlighting its crucial role in preventing cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor suppressor genes (TSGs) are critical in cancer development, particularly in nasopharyngeal carcinoma (NPC).
- Aberrant signaling pathways, including NF-κB, are frequently implicated in tumor progression and angiogenesis.
- IKBB, an inhibitor of NF-κB, was identified as a potential TSG in NPC, but its suppressive role requires further elucidation.
Purpose of the Study:
- To investigate the tumor suppressive role of IKBB in nasopharyngeal carcinoma (NPC).
- To elucidate the mechanisms by which IKBB inhibits NPC progression, focusing on angiogenesis and the NF-κB pathway.
Main Methods:
- Functional complementation studies using microcell-mediated chromosome transfer.
- Analysis of IKBB expression levels in NPC tumor tissues.
- Perturbation studies assessing the impact of IKBB on tumor formation, cell migration, and angiogenesis.
Main Results:
- IKBB was found to be silenced in the majority of NPC tumor tissues across all stages.
- IKBB's suppressive role was confirmed through its effects on tumor formation, cell migration, and angiogenesis.
- IKBB downregulates proangiogenic factors (Rantes, Upar, IL6, IL8) at the transcriptional level, affecting the tumor microenvironment ('soil').
Conclusions:
- This study establishes IKBB as a novel tumor suppressive gene in NPC.
- IKBB abrogates angiogenesis in NPC by inhibiting the NF-κB signaling pathway.
- The mechanism may involve crosstalk with the Akt/Gsk3β signaling pathway.
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