Stem cells (Dayton, Ohio)Mar 15, 2012

Blocking Polo-like kinase 1 kills aggressive brain tumor cells partly by reducing SOX2 and slows tumor growth in mice

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 4, 2026

Abstract

Polo-like kinase 1 (PLK1) is expressed 110-470 times more in brain tumor initiating cells compared to normal human astrocytes.

High PLK1 expression in glioblastoma multiforme (GBM) tumors is associated with poorer survival rates.
PLK1 is crucial for the survival of brain tumor initiating cells, which are linked to treatment resistance.
Inhibition of PLK1 using the drug BI2536 suppresses growth and induces cell death in brain tumor cells.
PLK1 inhibition leads to G(2) /M cell cycle arrest and reduces the expression of SOX2, a marker for neural stem cells.
Loss of PLK1 activity promotes differentiation of brain tumor cells, indicated by increased levels of glial fibrillary acidic protein.
BI2536 shows effectiveness in delaying tumor growth in an orthotopic brain tumor model.

Simplified

Glioblastoma multiforme (GBM) ranks among the deadliest types of cancer and given these new therapies are urgently needed. To identify molecular targets, we queried a microarray profiling 467 human GBMs and discovered that polo-like kinase 1 (PLK1) was highly expressed in these tumors and that it clustered with the proliferative subtype. Patients with PLK1-high tumors were more likely to die from their disease suggesting that current therapies are inactive against such tumors. This prompted us to examine its expression in brain tumor initiating cells (BTICs) given their association with treatment failure. BTICs isolated from patients expressed 110-470 times more PLK1 than normal human astrocytes. Moreover, BTICs rely on PLK1 for survival because the PLK1 inhibitor BI2536 inhibited their growth in tumorsphere cultures. PLK1 inhibition suppressed growth, caused G(2) /M arrest, induced apoptosis, and reduced the expression of SOX2, a marker of neural stem cells, in SF188 cells. Consistent with SOX2 inhibition, the loss of PLK1 activity caused the cells to differentiate based on elevated levels of glial fibrillary acidic protein and changes in cellular morphology. We then knocked glial fibrillary acidic protein (GFAP) down SOX2 with siRNA and showed that it too inhibited cell growth and induced cell death. Likewise, in U251 cells, PLK1 inhibition suppressed cell growth, downregulated SOX2, and induced cell death. Furthermore, BI2536 delayed tumor growth of U251 cells in an orthotopic brain tumor model, demonstrating that the drug is active against GBM. In conclusion, PLK1 level is elevated in GBM and its inhibition restricts the growth of brain cancer cells.

Full Text

Full text is available at the source.

View Full Text ↗

Blocking Polo-like kinase 1 kills aggressive brain tumor cells partly by reducing SOX2 and slows tumor growth in mice

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief