Aberrant Notch signaling in glioblastoma stem cells contributes to tumor recurrence and invasion

• Published in: Molecular medicine reports Vol. 14; no. 2; pp. 1263 - 1268
• Main Authors: Yu, Jian-Bo, Jiang, Hao, Zhan, Ren-Ya
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.08.2016; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: adenosine triphosphate-binding cassette transporters; Adolescent; Adult; anti-cancer drug; Apoptosis; Brain cancer; Cancer; cancer stem cells; Cancer therapies; Care and treatment; Cell division; Cell Self Renewal; Cell surface; Cellular signal transduction; Chemoresistance; Chemotherapy; Development and progression; Drug delivery; Drug development; Drug resistance; Drug Resistance, Neoplasm - genetics; Drug targeting; Female; Gene Expression; Genetic aspects; Glioblastoma; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma multiforme; Growth factors; Health aspects; Humans; Innovations; Intracellular signalling; Laboratories; Male; Medical prognosis; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Notch1; Notch1 protein; Oct-4 protein; Octamer Transcription Factor-3 - genetics; Octamer Transcription Factor-3 - metabolism; Patients; Proteins; Receptor, Notch1 - genetics; Receptor, Notch1 - metabolism; RNA Interference; RNA, Small Interfering - genetics; RNA-mediated interference; Signal Transduction; SOXB1 Transcription Factors - genetics; SOXB1 Transcription Factors - metabolism; Stem cells; Studies; tumor recurrence; Tumors; Young Adult; United States > US
• ISSN: 1791-2997; 1791-3004
• DOI: 10.3892/mmr.2016.5391

Upregulation of the Notch signaling pathway in cancer stem cells and side population (SP) cells has a major role in maintenance, self-renewal and chemoresistance. The present study isolated a cancer stem cell-like SP accounting for 4.1% of a glioblastoma cell population using a Hoechst 33342 dye exclusion assay. In this glioblastoma SP, the expression of of Notch1 signaling proteins Notch1 intracellular domain and Hes-1 was markedly upregulated. Furthermore, knockdown of Notch1 by RNA interference significantly diminished the neurosphere formation ability, self-renewal and chemo-resistance of the SP cells. In addition, the expression of the stem-cell surface genes Oct-4, Sox2 and Nanog in SP cells was significantly reduced and the sensitivity to the SP cells to chemotherapeutics was enhanced following Notch1 knockdown. In conclusion, the results of the present study suggested that upregulation of Notch1 is involved in the chemotherapy resistance and tumor recurrence of glioblastoma. Hence, the development of novel anti-cancer drugs targeting the Notch1 signaling pathway may be a promising strategy for curing glioblastoma.