Jul 17, 2019

Notch pathway in ependymoma RELA-fused subgroup: upregulation and association with cancer stem cells markers expression

Cancer Gene Therapy
Taciani de Almeida MagalhãesKleiton Silva Borges

Abstract

RELA-fused supratentorial (ST) ependymoma (EPN) is an aggressive subgroup with poor prognosis. Considering the putative role of Notch signaling in the maintenance of the cancer stem cells (CSC) phenotype in RELA-fused EPN, we investigated the expression of Notch pathway and its target genes in this subgroup. We also evaluated the effects of two Notch inhibitors (DAPT and RO4929097) on cell proliferation, apoptosis, colony formation, and CSCs markers gene expression on EPN cell line of the RELA-fused subgroup (BXD-1425). In addition, in silico signatures of the Notch genes and CSCs markers were analyzed on a large clinical dataset from GSE64415 study. We found that among the ST-EPN subgroups the Notch signaling (NOTCH1, JAG1, JAG2, and HES4) is specifically activated in the ST-EPN-RELA. Furthermore, treatment of the RELA-fused EPN cell line with the Notch inhibitors impaired the Notch signaling expression and revealed that Notch axis is not essential for cell proliferation and survival in this setting. NOTCH1 expression in ST-EPN was correlated with the CSCs markers VEGFA and L1CAM overexpression and JAG1 expression was correlated with the CCND1 and CDK6 overexpression. In addition, in vitro treatment with Notch inhibitors induc...Continue Reading

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Mentioned in this Paper

Biological Markers
Study
Biochemical Pathway
HES4
Phenylphosphonothioic Acid, 2-Ethyl 2-(4-Nitrophenyl) Ester
Genes
Tumor Markers, Biological
24-diamino-5-phenylthiazole
CDK6
Inhibitors

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