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

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

  • Cancers (Basel). 2021 Dec 29;14(1):151. doi: 10.3390/cancers14010151.
Gavin D Garland 1,  Stephen P Ducray 1,  Leila Jahangiri 1 2,  Perla Pucci 1,  G A Amos Burke 3,  Jack Monahan 4,  Raymond Lai 5,  Olaf Merkel 6,  Ana-Iris Schiefer 6,  Lukas Kenner 6 7 8 9,  Andrew J Bannister 10,  Suzanne D Turner 1 11
Affiliations

Affiliations

  • 1 Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK.
  • 2 Department of Life Sciences, Birmingham City University, Birmingham B15 3TN, UK.
  • 3 Department of Paediatric Oncology, Cambridge University Hospital NHS Trust, Cambridge CB5 8PD, UK.
  • 4 The European Bioinformatics Institute (EMBL EBI), Wellcome Genome Campus, Cambridge CB10 1SA, UK.
  • 5 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
  • 6 Department of Pathology, Medical University Vienna, 1090 Vienna, Austria.
  • 7 Unit of Pathology of Laboratory Animals, University of Veterinary Medicine Vienna, 1210 Vienna, Austria.
  • 8 CBMed, 8010 Graz, Austria.
  • 9 Christian Doppler Laboratory of Applied Metabolomics (CDL-AM), Medical University Vienna, 1090 Vienna, Austria.
  • 10 The Gurdon Institute, Cambridge CB2 1QN, UK.
  • 11 Central European Institute of Technology (CEITEC), Masaryk University, 601 77 Brno, Czech Republic.
PMID: 35008316 DOI: 10.3390/cancers14010151
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.

Keywords

ALCL; Brg1; NPM-ALK.

Figures
Products