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Updated: Jun 28, 2026
Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
Published on: September 1, 2010
Targeting the PI3K p110alpha isoform inhibits medulloblastoma proliferation, chemoresistance, and migration
Ana S Guerreiro1, Sarah Fattet, Barbara Fischer
1Department of Oncology, University Children's Hospital Zurich, Zurich, Switzerland.
Purpose:
The phosphoinositide 3-kinase (PI3K)/Akt pathway is frequently activated in human cancer and plays a crucial role in medulloblastoma biology. We were interested in gaining further insight into the potential of targeting PI3K/Akt signaling as a novel antiproliferative approach in medulloblastoma.
Experimental Design:
The expression pattern and functions of class I(A) PI3K isoforms were investigated in medulloblastoma tumour samples and cell lines. Effects on cell survival and downstream signaling were analyzed following down-regulation of p110alpha, p110beta, or p110delta by means of RNA interference or inhibition with isoform-specific PI3K inhibitors.
Results:
Overexpression of the catalytic p110alpha isoform was detected in a panel of primary medulloblastoma samples and cell lines compared with normal brain tissue. Down-regulation of p110alpha expression by RNA interference impaired the growth of medulloblastoma cells, induced apoptosis, and led to decreased migratory capacity of the cells. This effect was selective, because RNA interference targeting of p110beta or p110delta did not result in a comparable impairment of DAOY cell survival. Isoform-specific p110alpha inhibitors also impaired medulloblastoma cell proliferation and sensitized the cells to chemotherapy. Medulloblastoma cells treated with p110alpha inhibitors further displayed reduced activation of Akt and the ribosomal protein S6 kinase in response to stimulation with hepatocyte growth factor and insulin-like growth factor-I.
Conclusions:
Together, our data reveal a novel function of p110alpha in medulloblastoma growth and survival.
Insights
Targeting the p110alpha isoform of phosphoinositide 3-kinase (PI3K) shows promise for treating medulloblastoma. Inhibiting p110alpha halts cancer growth, induces apoptosis, and reduces cell migration in medulloblastoma.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The phosphoinositide 3-kinase (PI3K)/Akt pathway is frequently activated in human cancers.
- This pathway plays a critical role in medulloblastoma biology.
Purpose of the Study:
- To investigate the potential of targeting the PI3K/Akt signaling pathway as a novel antiproliferative strategy for medulloblastoma.
- To gain further insight into the role of PI3K isoforms in medulloblastoma.
Main Methods:
- Investigated expression patterns and functions of class I(A) PI3K isoforms in medulloblastoma samples and cell lines.
- Analyzed effects on cell survival and downstream signaling via RNA interference or isoform-specific inhibitors targeting p110alpha, p110beta, or p110delta.
Main Results:
- Overexpression of the catalytic p110alpha isoform was observed in medulloblastoma compared to normal brain tissue.
- Down-regulation of p110alpha impaired medulloblastoma cell growth, induced apoptosis, and reduced migration.
- Isoform-specific p110alpha inhibitors reduced proliferation, sensitized cells to chemotherapy, and decreased Akt/S6K activation.
Conclusions:
- The p110alpha isoform has a novel and significant function in medulloblastoma growth and survival.
- Targeting p110alpha represents a potential therapeutic strategy for medulloblastoma.
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