BCL-3 promotes a cancer stem cell phenotype by enhancing β-catenin signalling in colorectal tumour cells.

Disease Models & Mechanisms
Danny N LeggeAnn C Williams

Abstract

To decrease bowel cancer incidence and improve survival, we need to understand the mechanisms that drive tumorigenesis. Recently, B-cell lymphoma 3 (BCL-3; a key regulator of NF-κB signalling) has been recognised as an important oncogenic player in solid tumours. Although reported to be overexpressed in a subset of colorectal cancers (CRCs), the role of BCL-3 expression in colorectal tumorigenesis remains poorly understood. Despite evidence in the literature that BCL-3 may interact with β-catenin, it is perhaps surprising, given the importance of deregulated Wnt/β-catenin/T-cell factor (TCF) signalling in colorectal carcinogenesis, that the functional significance of this interaction is not known. Here, we show for the first time that BCL-3 acts as a co-activator of β-catenin/TCF-mediated transcriptional activity in CRC cell lines and that this interaction is important for Wnt-regulated intestinal stem cell gene expression. We demonstrate that targeting BCL-3 expression (using RNA interference) reduced β-catenin/TCF-dependent transcription and the expression of intestinal stem cell genes LGR5 and ASCL2 In contrast, the expression of canonical Wnt targets Myc and cyclin D1 remained unchanged. Furthermore, we show that BCL-3 incr...Continue Reading

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Citations

Apr 30, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Yue XieXinying Wang
Jan 21, 2020·Carcinogenesis·Daniel J TurnhamRichard W E Clarkson
Aug 28, 2020·Frontiers in Immunology·Lia WalcherUta Kossatz-Boehlert
Apr 23, 2020·International Journal of Oncology·Tracey Jane CollardAnn Caroline Williams
May 2, 2020·Signal Transduction and Targeted Therapy·Xi ChenXiaoren Zhang
Aug 24, 2021·Frontiers in Oncology·Sheila Coelho Soares-LimaLuis Felipe Ribeiro Pinto

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Methods Mentioned

BETA
transfection
immunoprecipitations
Co-IPs
Co-IP
PCR
nuclear translocation
immunoprecipitation
ChIP-seq
ChIP
acetylation

Software Mentioned

Matlab
TOPFlash
Leica LAS - X

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