Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age

Seaton, Gillian, Smith, Hannah, Brancale, Andrea, Westwell, Andrew D. ORCID: https://orcid.org/0000-0002-5166-9236 and Clarkson, Richard ORCID: https://orcid.org/0000-0001-7389-8673 2024. Multifaceted roles for BCL3 in cancer: a proto-oncogene comes of age. Molecular Cancer 23 (1) , 7. 10.1186/s12943-023-01922-8

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Abstract

In the early 1990’s a group of unrelated genes were identified from the sites of recurring translocations in B-cell lymphomas. Despite sharing the nomenclature ‘Bcl’, and an association with blood-borne cancer, these genes have unrelated functions. Of these genes, BCL2 is best known as a key cancer target involved in the regulation of caspases and other cell viability mechanisms. BCL3 on the other hand was originally identified as a non-canonical regulator of NF-kB transcription factor pathways – a signaling mechanism associated with important cell outcomes including many of the hallmarks of cancer. Most of the early investigations into BCL3 function have since focused on its role in NF-kB mediated cell proliferation, inflammation/immunity and cancer. However, recent evidence is coming to light that this protein directly interacts with and modulates a number of other signaling pathways including DNA damage repair, WNT/β-catenin, AKT, TGFβ/SMAD3 and STAT3 – all of which have key roles in cancer development, metastatic progression and treatment of solid tumours. Here we review the direct evidence demonstrating BCL3’s central role in a transcriptional network of signaling pathways that modulate cancer biology and treatment response in a range of solid tumour types and propose common mechanisms of action of BCL3 which may be exploited in the future to target its oncogenic effects for patient benefit.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Biosciences Pharmacy European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	BioMed Central
ISSN:	1476-4598
Date of First Compliant Deposit:	9 January 2024
Date of Acceptance:	20 December 2023
Last Modified:	19 Jan 2024 12:15
URI:	https://orca.cardiff.ac.uk/id/eprint/165370

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