Targeting class IA PI3K isoforms selectively impairs cell growth, survival, and migration in glioblastoma.

Höland, Katrin; Boller, Danielle; Hagel, Christian; Dolski, Silvia; Treszl, András; Pardo, Olivier E.; Cwiek, Paulina; Salm, Fabiana; Leni, Zaira; Shepherd, Peter R; Styp-Rekowska, Beata; Djonov, Valentin; von Bueren, André O.; Frei, Karl; Arcaro, Alexandre (2014). Targeting class IA PI3K isoforms selectively impairs cell growth, survival, and migration in glioblastoma. PLoS ONE, 9(4), e94132. Public Library of Science 10.1371/journal.pone.0094132

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hämatologie / Onkologie (Pädiatrie)

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology

UniBE Contributor:

Höland, Katrin; Cwiek, Paulina; Salm, Fabiana; Leni, Zaira; Djonov, Valentin and Arcaro, Alexandre

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Language:

English

Submitter:

André Schaller

Date Deposited:

05 Feb 2015 11:56

Last Modified:

05 Feb 2015 11:56

Publisher DOI:

10.1371/journal.pone.0094132

PubMed ID:

24718026

BORIS DOI:

10.7892/boris.62497

URI:

https://boris.unibe.ch/id/eprint/62497

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