BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL

Garland, Gavin D. and Ducray, Stephen P. and Jahangiri, Leila and Pucci, Perla and Amos Burke, G. A. and Monahan, Jack and Lai, Raymond and Merkel, Olaf and Schiefer, Ana-Iris and Kenner, Lukas and Bannister, Andrew J. and Turner, Suzanne D. (2021) BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL. Cancers, 14 (1). e151. ISSN 2072-6694

	Archive additional-files.zip - Additional Metadata Available under License Creative Commons Attribution. Download (1MB)
Preview	Text cancers-14-00151-v3.pdf - Published Version Available under License Creative Commons Attribution. Download (3MB)

Official URL: https://www.mdpi.com/2072-6694/14/1/151

Abstract

Anaplastic large-cell lymphoma (ALCL) is a T-cell malignancy driven in many cases by the product of a chromosomal translocation, nucleophosmin−anaplastic lymphoma kinase (NPM-ALK). NPM-ALK activates a plethora of pathways that drive the hallmarks of cancer, largely signalling pathways normally associated with cytokine and/or T-cell receptor-induced signalling. However, NPM-ALK is also located in the nucleus and its functions in this cellular compartment for the most part remain to be determined. We show that ALCL cell lines and primary patient tumours express the transcriptional activator BRG1 in a NPM-ALK-dependent manner. NPM-ALK regulates expression of BRG1 by post-translational mechanisms dependent on its kinase activity, protecting it from proteasomal degradation. Furthermore, we show that BRG1 drives a transcriptional programme associated with cell cycle progression. In turn, inhibition of BRG1 expression with specific shRNA decreases cell viability, suggesting that it may represent a key therapeutic target for the treatment of ALCL.

Item Type:	Article
Additional Information:	From MDPI via Jisc Publications Router History: accepted 28-12-2021; pub-electronic 29-12-2021. ** Licence for this article: https://creativecommons.org/licenses/by/4.0/
Identification Number:	10.3390/cancers14010151
Dates:	Date Event 28 December 2021 Accepted 29 December 2021 Published Online
Uncontrolled Keywords:	NPM-ALK, ALCL, Brg1
Subjects:	CAH01 - medicine and dentistry > CAH01-01 - medicine and dentistry > CAH01-01-01 - medical sciences (non-specific)
Divisions:	Faculty of Health, Education and Life Sciences > Centre for Life and Sport Sciences (C-LASS)
SWORD Depositor:	JISC PubRouter
Depositing User:	JISC PubRouter
Date Deposited:	17 Jan 2022 14:22
Last Modified:	17 Jan 2022 14:22
URI:	https://www.open-access.bcu.ac.uk/id/eprint/12611