TY - JOUR
T1 - Glycerophosphodiesterase GDE2 Promotes Neuroblastoma Differentiation through Glypican Release and Is a Marker of Clinical Outcome
AU - Matas-Rico, Elisa
AU - van Veen, Michiel
AU - Leyton-Puig, Daniela
AU - van den Berg, Jeroen
AU - Koster, Jan
AU - Kedziora, Katarzyna M.
AU - Molenaar, Bas
AU - Weerts, Marjolein J. A.
AU - de Rink, Iris
AU - Medema, René H.
AU - Giepmans, Ben N. G.
AU - Perrakis, Anastassis
AU - Jalink, Kees
AU - Versteeg, Rogier
AU - Moolenaar, Wouter H.
PY - 2016
Y1 - 2016
N2 - 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
AB - 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
U2 - https://doi.org/10.1016/j.ccell.2016.08.016
DO - https://doi.org/10.1016/j.ccell.2016.08.016
M3 - Article
C2 - 27693046
SN - 1535-6108
VL - 30
SP - 548
EP - 562
JO - Cancer cell
JF - Cancer cell
IS - 4
ER -