%0 Journal Article
%T Targeting Class IA PI3K Isoforms Selectively Impairs Cell Growth, Survival, and Migration in Glioblastoma
%A Katrin H£¿land
%A Danielle Boller
%A Christian Hagel
%A Silvia Dolski
%A Andr¨¢s Treszl
%A Olivier E. Pardo
%A Paulina £¿wiek
%A Fabiana Salm
%A Zaira Leni
%A Peter R. Shepherd
%A Beata Styp-Rekowska
%A Valentin Djonov
%A Andr¨¦ O. von Bueren
%A Karl Frei
%A Alexandre Arcaro
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0094132
%X 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 p110¦Á was detected in a panel of glioblastoma patient samples. In contrast, PI3K p110¦Â expression was only rarely detected in glioblastoma patient samples. The expression of a module comprising the epidermal growth factor receptor (EGFR)/PI3K p110¦Á/phosphorylated ribosomal S6 protein (p-S6) was correlated with shorter patient survival. Inhibition of PI3K p110¦Á activity impaired the anchorage-dependent growth of glioblastoma cells and induced tumor regression in vivo. Inhibition of PI3K p110¦Á or PI3K p110¦Â 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 p110¦Ä did not result in a comparable impairment of glioblastoma tumorigenic properties. Together, our data reveal that drugs targeting PI3K p110¦Á can reduce growth in a subset of glioblastoma tumors characterized by the expression of EGFR/PI3K p110¦Á/p-S6.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0094132