Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/44815
Title: BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma
Authors: Lazarus, KA
Hadi, F
Zambon, E
Bach, K
Santolla, M-F
Watson, JK
Correia, LL
Das, M
Ugur, R
Pensa, S
Becker, L
Campos, LS
Ladds, G
Liu, P
Evan, G
McCaughan, FM
Le Quesne, J
Lee, J-H
Calado, D
Khaled, WT
First Published: 20-Aug-2018
Publisher: Nature Research (part of Springer Nature)
Citation: Nature Communications, 2018, 9, Article number: 3327
Abstract: Patients diagnosed with lung squamous cell carcinoma (LUSC) have limited targeted therapies. We report here the identification and characterisation of BCL11A, as a LUSC oncogene. Analysis of cancer genomics datasets revealed BCL11A to be upregulated in LUSC but not in lung adenocarcinoma (LUAD). Experimentally we demonstrate that non-physiological levels of BCL11A in vitro and in vivo promote squamous-like phenotypes, while its knockdown abolishes xenograft tumour formation. At the molecular level we found that BCL11A is transcriptionally regulated by SOX2 and is required for its oncogenic functions. Furthermore, we show that BCL11A and SOX2 regulate the expression of several transcription factors, including SETD8. We demonstrate that shRNA-mediated or pharmacological inhibition of SETD8 selectively inhibits LUSC growth. Collectively, our study indicates that BCL11A is integral to LUSC pathology and highlights the disruption of the BCL11A–SOX2 transcriptional programme as a novel candidate for drug development.
DOI Link: 10.1038/s41467-018-05790-5
ISSN: 2041-1723
Links: https://www.nature.com/articles/s41467-018-05790-5
http://hdl.handle.net/2381/44815
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2018. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: Code availability Source code will be available on request. Data availability The Chipseq data is available from ArrayExpress (accession numbers: # E-MTAB-6958) . The authors declare that all remaining data supporting the findings of this study are available within the article and its Supplementary Information files or from the authors upon request.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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