GRP78 is overexpressed in glioblastomas and regulates glioma cell growth and apoptosis

Hae Kyung Lee, Cunli Xiang, Simona Cazacu, Susan Finniss, Gila Kazimirsky, Nancy Lemke, Norman L. Lehman, Sandra A. Rempel, Tom Mikkelsen, Chaya Brodie

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

We characterized the expression and function of the endoplasmic reticulum protein GRP78 in glial tumors. GRP78 is highly expressed in glioblastomas but not in oligodendrogliomas, and its expression is inversely correlated with median patient survival. Overexpression of GRP78 in glioma cells decreases caspase 7 activation and renders the cells resistant to etoposide- and cisplatin- induced apoptosis, whereas silencing of GRP78 decreases cell growth and sensitizes glioma cells to etoposide, cisplatin, and γ-radiation. Thus, GRP78 contributes to the increased apoptosis resistance and growth of glioma cells and may provide a target for enhancing the therapeutic responsiveness of these tumors.

Original languageEnglish
Pages (from-to)236-243
Number of pages8
JournalNeuro-Oncology
Volume10
Issue number3
DOIs
StatePublished - Jun 2008
Externally publishedYes

Keywords

  • Apoptosis
  • Caspase 7
  • GRP78
  • Glioblastoma
  • Survival

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