Aberrant Notch signaling in glioblastoma stem cells contributes to tumor recurrence and invasion.
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 chemoresistance 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.
Department of Neurosurgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Jian-Bo
JB
Yu
Department of Neurosurgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Hao
H
Jiang
Department of Neurosurgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
Ren-Ya
RY
Zhan
D000293:Adolescent; D000328:Adult; D000066673:Cell Self Renewal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D055815:Young Adult
D050814:Octamer Transcription Factor-3; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D055748:SOXB1 Transcription Factors