Serine-Threonine Kinase Receptor Associate Protein (STRAP) confers an aggressive phenotype in neuroblastoma via regulation of Focal Adhesion Kinase (FAK)

Laura V. Bownes; Raoud Marayati; Colin H. Quinn; Sara C. Hutchins; Jerry E. Stewart; Joshua C. Anderson; Christopher D. Willey; Pran K. Datta; Elizabeth A. Beierle

doi:10.1016/j.jpedsurg.2022.01.064

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Serine-Threonine Kinase Receptor Associate Protein (STRAP) confers an aggressive phenotype in neuroblastoma via regulation of Focal Adhesion Kinase (FAK)

Journal article

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Serine-Threonine Kinase Receptor Associate Protein (STRAP) confers an aggressive phenotype in neuroblastoma via regulation of Focal Adhesion Kinase (FAK)

Laura V. Bownes, Raoud Marayati, Colin H. Quinn, Sara C. Hutchins, Jerry E. Stewart, Joshua C. Anderson, Christopher D. Willey, Pran K. Datta and Elizabeth A. Beierle

Journal of pediatric surgery, Vol.57(6), pp.1026-1032

06/01/2022

DOI: 10.1016/j.jpedsurg.2022.01.064

PMCID: PMC9119921

PMID: 35272839

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Abstract

Serine-threonine kinase receptor associated protein (STRAP), a scaffolding protein, is upregulated in many solid tumors. As such, we hypothesized that STRAP may be overexpressed in neuroblastoma tumors and may play a role in neuroblastoma tumor progression. We examined two publicly available neuroblastoma patient databases, GSE49710 (n = 498) and GSE49711 (n = 498), to investigate STRAP expression in human specimens. SK-N-AS and SK-N-BE(2) human neuroblastoma cell lines were stably transfected with STRAP overexpression (OE) plasmid, and their resulting phenotype studied. PamChip® kinomic peptide microarray evaluated the effects of STRAP overexpression on kinase activation. In human specimens, higher STRAP expression correlated with high-risk disease, unfavorable histology, and decreased overall neuroblastoma patient survival. STRAP OE in neuroblastoma cell lines led to increased proliferation, growth, supported a stem-like phenotype and activated downstream FAK targets. When FAK was targeted with the small molecule FAK inhibitor, PF-573,228, STRAP OE neuroblastoma cells had significantly decreased growth compared to control empty vector cells. Increased STRAP expression in neuroblastoma was associated with unfavorable tumor characteristics. STRAP OE resulted in increased kinomic activity of FAK. These findings suggest that the poorer outcomes in neuroblastoma tumors associated with STRAP overexpression may be secondary to FAK activation.

FAK

Focal adhesion kinase

Neuroblastoma

Serine-threonine kinase receptor-associated protein

STRAP

Details

Title: Subtitle: Serine-Threonine Kinase Receptor Associate Protein (STRAP) confers an aggressive phenotype in neuroblastoma via regulation of Focal Adhesion Kinase (FAK)
Creators: Laura V. Bownes - University of Alabama at Birmingham
Raoud Marayati - University of Alabama at Birmingham
Colin H. Quinn - University of Alabama at Birmingham
Sara C. Hutchins - University of Alabama at Birmingham
Jerry E. Stewart - University of Alabama at Birmingham
Joshua C. Anderson - University of Alabama at Birmingham
Christopher D. Willey - University of Alabama at Birmingham
Pran K. Datta - University of Alabama at Birmingham
Elizabeth A. Beierle - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: Journal of pediatric surgery, Vol.57(6), pp.1026-1032
DOI: 10.1016/j.jpedsurg.2022.01.064
PMID: 35272839
PMCID: PMC9119921
NLM abbreviation: J Pediatr Surg
ISSN: 0022-3468
eISSN: 1531-5037
Publisher: Elsevier Inc
Number of pages: 7
Language: English
Date published: 06/01/2022
Academic Unit: Stead Family Department of Pediatrics; Hematology/Oncology
Record Identifier: 9984701543702771

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