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BCL–3 promotes cyclooxygenase–2/prostaglandin E2 signalling in colorectal cancer

Collard, Tracey Jane; Fallatah, Hafsah Mohammed; Greenhough, Alexander; Paraskeva, Christos; Williams, Ann Caroline

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Authors

Tracey Jane Collard

Hafsah Mohammed Fallatah

Christos Paraskeva

Ann Caroline Williams



Abstract

First discovered as an oncogene in leukaemia, recent reports highlight an emerging role for the proto-oncogene BCL-3 in solid tumours. Importantly, BCL-3 expression is upregulated in >30% of colorectal cancer cases and is reported to be associated with a poor prognosis. However, the mechanism by which BCL-3 regulates tumorigenesis in the large intestine is yet to be fully elucidated. In the present study, it was shown for the first time that knocking down BCL–3 expression suppressed cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) signalling in colorectal cancer cells, a pathway known to drive several of the hallmarks of cancer. RNAi-mediated suppression of BCL-3 expression decreased COX-2 expression in colorectal cancer cells both at the mRNA and protein level. This reduction in COX–2 expression resulted in a significant and functional reduction (30-50%) in the quantity of pro-tumorigenic PGE2 produced by the cancer cells, as shown by enzyme linked immunoassays and medium exchange experiments. In addition, inhibition of BCL-3 expression also significantly suppressed cytokine–induced (TNF–α or IL-1β) COX-2 expression. Taken together, the results of the present study identified a novel role for BCL–3 in colorectal cancer and suggested that expression of BCL-3 may be a key determinant in the COX–2–meditated response to inflammatory cytokines in colorectal tumour cells. These results suggest that targeting BCL-3 to suppress PGE2 synthesis may represent an alternative or complementary approach to using non-steroidal anti-inflammatory drugs [(NSAIDs), which inhibit cyclooxygenase activity and suppress the conversion of arachidonic acid to prostaglandin], for prevention and/or recurrence in PGE2-driven tumorigenesis.

Citation

Collard, T. J., Fallatah, H. M., Greenhough, A., Paraskeva, C., & Williams, A. C. (2020). BCL–3 promotes cyclooxygenase–2/prostaglandin E2 signalling in colorectal cancer. International Journal of Oncology, 56(5), 1304-1313. https://doi.org/10.3892/ijo.2020.5013

Journal Article Type Article
Acceptance Date Mar 16, 2020
Online Publication Date Mar 16, 2020
Publication Date May 1, 2020
Deposit Date Jan 19, 2021
Publicly Available Date Mar 17, 2021
Journal International Journal of Oncology
Print ISSN 1019-6439
Electronic ISSN 1791-2423
Publisher Spandidos Publications
Peer Reviewed Peer Reviewed
Volume 56
Issue 5
Pages 1304-1313
DOI https://doi.org/10.3892/ijo.2020.5013
Public URL https://uwe-repository.worktribe.com/output/7002184

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