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

Author(s)

de Almeida Magalhaes, Taciani ^[1] ; Cruzeiro, Gustavo Alencastro Veiga ^{[2, 1]} ; de Sousa, Graziella Ribeiro ^{[1, 3]} ; da Silva, Keteryne Rodrigues ^{[1, 3]} ; Lira, Regia Caroline Peixoto ^{[2, 1]} ; Scrideli, Carlos Alberto ^{[2, 1]} ; Tone, Luiz Gonzaga ^{[2, 1, 3]} ; Valera, Elvis Terci ^{[2, 1]} ; Borges, Kleiton Silva ^[2]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Ribeirao Preto, SP - Brazil

^[3] Borges, Kleiton Silva, Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pediat, Ribeirao Preto, SP, Brazil.de Almeida Magalhaes, Taciani, Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Cancer Gene Therapy; v. 27, n. 6, p. 509-512, JUN 2020.
• Web of Science Citations: 0

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, andHES4) 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.NOTCH1expression in ST-EPN was correlated with the CSCs markersVEGFAandL1CAMoverexpression andJAG1expression was correlated with theCCND1andCDK6overexpression. In addition, in vitro treatment with Notch inhibitors induced downregulation of CSCs markers. These findings indicate that Notch signaling can be involved in the ST-EPN-RELA CSCs maintenance by modulating the expression of genes responsible for cell phenotype and cell fate. (AU)

• FAPESP's process: 14/20341-0 - Interactions between emerging therapeutic targets and developmental pathways associated with tumorigenesis: emphasis on pediatric malignancies
• Grantee: Luiz Gonzaga Tone
• Support Opportunities: Research Projects - Thematic Grants