Inhibition of PIM Kinases Promotes Neuroblastoma Cell Differentiation to a Neuronal Phenotype

Janet R. Julson; Colin H. Quinn; Laura V. Bownes; Sara C. Hutchins; Jerry E. Stewart; Jamie Aye; Karina J. Yoon; Elizabeth A. Beierle

doi:10.1016/j.jpedsurg.2023.02.018

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Inhibition of PIM Kinases Promotes Neuroblastoma Cell Differentiation to a Neuronal Phenotype

Journal article

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Inhibition of PIM Kinases Promotes Neuroblastoma Cell Differentiation to a Neuronal Phenotype

Janet R. Julson, Colin H. Quinn, Laura V. Bownes, Sara C. Hutchins, Jerry E. Stewart, Jamie Aye, Karina J. Yoon and Elizabeth A. Beierle

Journal of pediatric surgery, Vol.58(6), pp.1155-1163

06/2023

DOI: 10.1016/j.jpedsurg.2023.02.018

PMCID: PMC10198809

PMID: 36907773

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Abstract

Neuroblastoma arises from aberrancies in neural stem cell differentiation. PIM kinases contribute to cancer formation, but their precise role in neuroblastoma tumorigenesis is poorly understood. In the current study, we evaluated the effects of PIM kinase inhibition on neuroblastoma differentiation. Versteeg database query assessed the correlation between PIM gene expression and the expression of neuronal stemness markers and relapse free survival. PIM kinases were inhibited with AZD1208. Viability, proliferation, motility were measured in established neuroblastoma cells lines and high-risk neuroblastoma patient-derived xenografts (PDXs). qPCR and flow cytometry detected changes in neuronal stemness marker expression after AZD1208 treatment. Database query showed increased levels of PIM1, PIM2, or PIM3 gene expression were associated with higher risk of recurrent or progressive neuroblastoma. Increased levels of PIM1 were associated with lower relapse free survival rates. Higher levels of PIM1 correlated with lower levels of neuronal stemness markers OCT4, NANOG, and SOX2. Treatment with AZD1208 resulted in increased expression of neuronal stemness markers. Inhibition of PIM kinases differentiated neuroblastoma cancer cells toward a neuronal phenotype. Differentiation is a key component of preventing neuroblastoma relapse or recurrence and PIM kinase inhibition provides a potential new therapeutic strategy for this disease. •PIM kinases are oncogenes implicated in numerous malignancies.•Knowledge about the role of PIM kinases in neuroblastoma is lacking.•Differentiation is a key component of neuroblastoma therapy to prevent relapse or recurrence.•PIM kinases serve as a novel potential therapeutic target to promote neuroblastoma differentiation.

AZD1208

Neuroblastoma

PIM kinase

Stem cell

Details

Title: Subtitle: Inhibition of PIM Kinases Promotes Neuroblastoma Cell Differentiation to a Neuronal Phenotype
Creators: Janet R. Julson - University of Alabama at Birmingham
Colin H. Quinn - University of Alabama at Birmingham
Laura V. Bownes - University of Alabama at Birmingham
Sara C. Hutchins - University of Alabama at Birmingham
Jerry E. Stewart - University of Alabama at Birmingham
Jamie Aye - University of Alabama at Birmingham
Karina J. Yoon - University of Alabama at Birmingham
Elizabeth A. Beierle - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: Journal of pediatric surgery, Vol.58(6), pp.1155-1163
DOI: 10.1016/j.jpedsurg.2023.02.018
PMID: 36907773
PMCID: PMC10198809
NLM abbreviation: J Pediatr Surg
ISSN: 0022-3468
eISSN: 1531-5037
Publisher: Elsevier Inc
Number of pages: 9
Language: English
Date published: 06/2023
Academic Unit: Stead Family Department of Pediatrics; Hematology/Oncology
Record Identifier: 9984701653902771

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