Targeting Class IA PI3K Isoforms Selectively Impairs Cell Growth, Survival, and Migration in Glioblastoma
- Link:
- Autor/in:
- Erscheinungsjahr:
- 2014
- Medientyp:
- Text
- Schlagworte:
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- dk/atira/pure/publikationen_lom_relevant/publikation_ist_nicht_scoring_relevant
- Hamburg Center of Neuroscience (HCNS)
- dk/atira/pure/keywords/workgroup/143
- AG Statistische Beratung (143)
- Beschreibung:
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The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is frequently activated in human cancer and plays a crucial role in glioblastoma biology. We were interested in gaining further insight into the potential of targeting PI3K isoforms as a novel anti-tumor approach in glioblastoma. Consistent expression of the PI3K catalytic isoform PI3K p110α was detected in a panel of glioblastoma patient samples. In contrast, PI3K p110β expression was only rarely detected in glioblastoma patient samples. The expression of a module comprising the epidermal growth factor receptor (EGFR)/PI3K p110α/phosphorylated ribosomal S6 protein (p-S6) was correlated with shorter patient survival. Inhibition of PI3K p110α activity impaired the anchorage-dependent growth of glioblastoma cells and induced tumor regression in vivo. Inhibition of PI3K p110α or PI3K p110β also led to impaired anchorage-independent growth, a decreased migratory capacity of glioblastoma cells, and reduced the activation of the Akt/mTOR pathway. These effects were selective, because targeting of PI3K p110δ did not result in a comparable impairment of glioblastoma tumorigenic properties. Together, our data reveal that drugs targeting PI3K p110α can reduce growth in a subset of glioblastoma tumors characterized by the expression of EGFR/PI3K p110α/p-S6.
- Lizenz:
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- info:eu-repo/semantics/openAccess
- Quellsystem:
- Forschungsinformationssystem des UKE
Interne Metadaten
- Quelldatensatz
- oai:pure.atira.dk:publications/dd84b8ec-6fc4-448d-9728-0db8326becc3