Journal
JOURNAL OF PEDIATRIC SURGERY
Volume 57, Issue 6, Pages 1026-1032Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.jpedsurg.2022.01.064
Keywords
Serine-threonine kinase receptor-associated protein; STRAP; Focal adhesion kinase; FAK; Neuroblastoma
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Funding
- National Institutes of Health [T32CA229102, 5T32GM008361, P30AR048311, P30AI27667]
- Veterans Affairs Merit Review Award [1I01BX005143]
- UABU54 Pilot Project [CA118948]
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The study found that increased expression of STRAP in neuroblastoma patients is associated with unfavorable tumor characteristics, and that overexpression of STRAP leads to increased proliferation and growth of neuroblastoma cells, activating the FAK signaling pathway.
Background: 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. Methods: 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 (R) kinomic peptide microarray evaluated the effects of STRAP overexpression on kinase activation. Results: 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. Conclusion: 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.
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