BRG1 and NPM-ALK Are Co-Regulated in Anaplastic Large-Cell Lymphoma; BRG1 Is a Potential Therapeutic Target in ALCL.
Gavin D GarlandStephen P DucrayLeila JahangiriPerla PucciG A Amos BurkeJack MonahanRaymond LaiOlaf MerkelAna-Iris SchieferLukas KennerAndrew J BannisterSuzanne D TurnerPublished in: Cancers (2021)
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.
Keyphrases
- acute myeloid leukemia
- advanced non small cell lung cancer
- cell cycle
- diffuse large b cell lymphoma
- poor prognosis
- single cell
- transcription factor
- gene expression
- cell proliferation
- cell therapy
- epidermal growth factor receptor
- binding protein
- tyrosine kinase
- randomized controlled trial
- risk assessment
- squamous cell carcinoma
- protein kinase
- mesenchymal stem cells
- oxidative stress
- dna methylation
- immune response
- high glucose
- inflammatory response
- endothelial cells
- combination therapy
- replacement therapy