Serine-Threonine Kinase Receptor Associate Protein (STRAP) Confers an Aggressive Phenotype in Neuroblastoma via Regulation of Focal Adhesion Kinase (FAK)
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Read the article on jpedsurg.org ↗Article · Feb 2022 · 1 min read
In brief
In brief
STRAP protein overexpression in neuroblastoma correlates with high-risk disease and poor survival by activating focal adhesion kinase (FAK) signaling pathways. Experimental models demonstrate that STRAP drives aggressive tumor behavior including increased proliferation and stem-like characteristics, which can be reversed with FAK inhibition.
Written by the GCMD Library team from the article.
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® 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.