BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma

Lazarus, K. A. et al. (2018) BCL11A interacts with SOX2 to control the expression of epigenetic regulators in lung squamous carcinoma. Nature Communications, 9(1), 3327. (doi: 10.1038/s41467-018-05790-5) (PMID:30127402) (PMCID:PMC6102279)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Le Quesne, Professor John
Authors: Lazarus, K. A., Hadi, F., Zambon, E., Bach, K., Santolla, M.-F., Watson, J. K., Correia, L. L., Das, M., Ugur, R., Pensa, S., Becker, L., Campos, L. S., Ladds, G., Liu, P., Evan, G. I., McCaughan, F. M., Le Quesne, J., Lee, J.-H., Calado, D., and Khaled, W. T.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:Nature Communications
Publisher:Nature
ISSN:2041-1723
Published Online:20 August 2018
Copyright Holders:Copyright © The Author(s) 2018.
First Published:First published in Nat Commun 9, 3327 (2018).
Publisher Policy:This is an Open Access article distributed under the terms of the Creative Commons Attribution License
Data DOI:10.1038/s41467- 018-05790-5

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