Abstract

Glioblastoma recurrence after aggressive therapy typically occurs within six months, and patients inevitably succumb to their disease. Tumor recurrence is driven by a subpopulation of cancer stem cells in glioblastoma (glioblastoma stem-like cells, GSCs), which exhibit resistance to cytotoxic therapies, compared to their non-stem-cell counterparts. Here, we show that the Cox-2 and Wnt signaling pathways are aberrantly activated in GSCs and interact to maintain the cancer stem cell identity. Cox-2 stimulates GSC self-renewal and proliferation through prostaglandin E2 (PGE2), which in turn activates the Wnt signaling pathway. Wnt signaling underlies PGE2-induced GSC selfrenewal and independently directs GSC self-renewal and proliferation. Inhibition of PGE2 enhances the effect of temozolomide on GSCs, but affords only a modest survival advantage in a xenograft model in the setting of COX-independent Wnt activation. Our findings uncover an aberrant positive feedback interaction between the Cox-2/PGE2 and Wnt pathways that mediates the stem-like state in glioblastoma.

Original languageEnglish
Pages (from-to)82217-82230
Number of pages14
JournalOncotarget
Volume8
Issue number47
DOIs
StatePublished - 2017

Keywords

  • Cancer stem cells
  • Cyclooxygenase
  • Glioblastoma
  • Prostaglandin E2
  • Wnt

Fingerprint

Dive into the research topics of 'Aberrantly activated Cox-2 and Wnt signaling interact to maintain cancer stem cells in glioblastoma'. Together they form a unique fingerprint.

Cite this