Cancer Cell
Volume 30, Issue 4, 10 October 2016, Pages 548-562
Journal home page for Cancer Cell

Article
Glycerophosphodiesterase GDE2 Promotes Neuroblastoma Differentiation through Glypican Release and Is a Marker of Clinical Outcome

https://doi.org/10.1016/j.ccell.2016.08.016Get rights and content
Under a Creative Commons license
open access

Highlights

  • GDE2 (GDPD5) induces differentiation of neuroblastoma cells

  • High GDPD5 expression strongly correlates with favorable clinical outcome

  • GDE2 activates Rac, inhibits neurite retraction, and alters gene expression

  • GDE2 acts by releasing GPI-anchored glypican-6 from the cell surface

Summary

Neuroblastoma is a pediatric embryonal malignancy characterized by impaired neuronal differentiation. A better understanding of neuroblastoma differentiation is essential for developing new therapeutic approaches. GDE2 (encoded by GDPD5) is a six-transmembrane-domain glycerophosphodiesterase that promotes embryonic neurogenesis. We find that high GDPD5 expression is strongly associated with favorable outcome in neuroblastoma. GDE2 induces differentiation of neuroblastoma cells, suppresses cell motility, and opposes RhoA-driven neurite retraction. GDE2 alters the Rac-RhoA activity balance and the expression of multiple differentiation-associated genes. Mechanistically, GDE2 acts by cleaving (in cis) and releasing glycosylphosphatidylinositol-anchored glypican-6, a putative co-receptor. A single point mutation in the ectodomain abolishes GDE2 function. Our results reveal GDE2 as a cell-autonomous inducer of neuroblastoma differentiation with prognostic significance and potential therapeutic value.

Cited by (0)

5

Present address: Department of Cell Biology, University Medical Center Groningen, 9713 AV Groningen, the Netherlands

6

Lead Contact