Abrogation of PIK3CA or PIK3R1 reduces proliferation, migration, and invasion in glioblastoma multiforme cells

Abstract

Glioblastoma multiforme (GBM) is a highly invasive and deadly brain tumor.  Tumor cell invasion makes complete surgical resection impossible and reduces the efficacy of other therapies.  Genome-wide analyses of mutations, copy-number changes, and expression patterns have provided new insights into genetic abnormalities common in GBM.  We analyzed published data and identified the invasion and motility pathways most frequently altered in GBM. These were most notably the focal adhesion and integrin signaling, and extracellular matrix interactions pathways.  We mapped alterations in each of these pathways and found that they included the catalytic PIK3CA and regulatory PIK3R1 subunit genes of the class IA PI3K.  Knockdown of either of these genes separately in GBM cell lines by lentiviral-mediated shRNA expression resulted in decreased proliferation, migration, and invasion in all lines tested.  FAK activity was reduced by knockdown of either PIK3CA or PIK3R1, and MMP2 levels were reduced by knockdown of PIK3R1.  We conclude that PIK3R1, like PIK3CA, is a potential therapeutic target in GBM and that it also influences tumor cell growth and motility.