Targeting Class I-A PI3K Isoforms Selectively Impairs Cell Growth, Survival, and Migration in Glioblastoma
2014 | journal article. A publication with affiliation to the University of Göttingen.
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Targeting Class I-A PI3K Isoforms Selectively Impairs Cell Growth, Survival, and Migration in Glioblastoma
Hoeland, K.; Boller, D.; Hagel, C.; Dolski, S.; Treszl, A.; Pardo, O. E. & Cwiek, P. et al. (2014)
PLoS ONE, 9(4) art. e94132. DOI: https://doi.org/10.1371/journal.pone.0094132
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Details
- Authors
- Hoeland, Katrin; Boller, Danielle; Hagel, Christian; Dolski, Silvia; Treszl, Andras; Pardo, Olivier E.; Cwiek, Paulina; Salm, Fabiana; Leni, Zaira; Shepherd, Peter R.; Styp-Rekowska, Beata; Djonov, Valentin; von Bueren, Andre Oscar; Frei, Karl; Arcaro, Alexandre
- Abstract
- 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 p11 alpha was detected in a panel of glioblastoma patient samples. In contrast, PI3K p11 beta expression was only rarely detected in glioblastoma patient samples. The expression of a module comprising the epidermal growth factor receptor (EGFR)/PI3K p110 alpha/phosphorylated ribosomal S6 protein (p-S6) was correlated with shorter patient survival. Inhibition of PI3K p11 alpha activity impaired the anchorage-dependent growth of glioblastoma cells and induced tumor regression in vivo. Inhibition of PI3K p11 alpha or PI3K p110 alpha 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 p11 delta d did not result in a comparable impairment of glioblastoma tumorigenic properties. Together, our data reveal that drugs targeting PI3K p110a can reduce growth in a subset of glioblastoma tumors characterized by the expression of EGFR/PI3K p110 alpha/p-S6.
- Issue Date
- 2014
- Status
- published
- Publisher
- Public Library Science
- Journal
- PLoS ONE
- ISSN
- 1932-6203