Wnt-5a gene expression in malignant human neuroblasts.
Neuroblastoma (NB), an embryonal malignancy, poses a major challenge in pediatric oncology for the treatment of disseminated forms. Here, we report the decrease of Wnt-5a gene expression in high-risk NB (HR-NB) as well as in cultured metastatic neuroblasts. Wnt-5a is a member of the Wnt signaling pathway which is mainly associated with patterning decisions in the embryonic nervous system. Moreover, Wnt-5a has been involved in metastatic melanoma progression and invasive ductal breast cancer via adhesion and migration alterations. As retinoic acid (RA) plays a major role in the neural crest induction and differentiation, we showed that RA reverses the aberrant negative regulation of Wnt-5a in metastatic neuroblasts. While beta-catenin expression remained unchanged, PKC-theta, a protein kinase C isoform, was evidenced to increase and parallel Wnt-5a level. For the first time, the involvement of Wnt-5a through the Wnt/calcium signaling is highlighted in the pathogenesis of a pediatric embryonal malignancy, NB.
Blanc
Etienne
E
Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Unité Mixte de Recherche 8126, IFR 54, 39, rue Camille Desmoulins, 94805 Villejuif Cedex, France.
Goldschneider
David
D
Douc-Rasy
Sétha
S
Bénard
Jean
J
Raguénez
Gilda
G
D002454:Cell Differentiation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009447:Neuroblastoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014212:Tretinoin / Q000494:pharmacology; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D000071818:Wnt-5a Protein
D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D014212:Tretinoin; D011493:Protein Kinase C