Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/12254
Title: The catalytic phosphoinositol 3-kinase isoform p110 delta is required for glioma cell migration and invasion
Authors: Luk, SK
Piekorz, RP
Nurnberg, B
To, SST 
Keywords: Phosphoinositide 3-kinase
P110 delta
Glioma
Migration
Invasion
Issue Date: 2012
Publisher: Pergamon Press
Source: European journal of cancer, 2012, v. 48, no. 1, p. 149-157 How to cite?
Journal: European journal of cancer 
Abstract: Glioblastoma multiforme (GBM) is a highly invasive and aggressive primary brain tumour in which loss of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a negative regulator of PI3K signalling, is a common feature. PTEN/PI3K/Akt signalling is involved in the regulation of proliferation, apoptosis and cell migration. Deregulation of PI3K signalling is considered an essential driver in gliomagenesis. However, the role of different PI3K isoforms in glioma is still largely unclear. Here we show that the catalytic PI3K isoform p110 delta is consistently expressed at a high level in various glioma cell lines. We used small interfering RNA to selectively deplete p110 delta and to determine its tumourigenic roles in PTEN-deficient cells. Interestingly, knockdown of p110 delta decreased the cell migration and invasion ability of all GBM cell lines tested. Mechanistically, p110 delta knockdown reduced the protein levels of focal adhesion kinase and cell division cycle 42, key regulators of cellular migration. In contrast, pharmacologic inhibition of p110 delta by IC87114 or CAL-101 also clearly impaired glioma cell migration but had no obvious effect on the invasion capacity thus pinpointing to possible kinase-dependent and -independent roles of p110 delta in glioma pathology. In summary, our data provide novel evidence that in glioma cells p110 delta is a key regulator of cell movement and thus may contribute to the highly invasive phenotype of GBM. Isoform specific targeting of PI3K delta may be beneficial in the treatment of glioblastoma multiforme by specifically inhibiting tumour cell migration capacity.
URI: http://hdl.handle.net/10397/12254
ISSN: 0959-8049
EISSN: 1879-0852
DOI: 10.1016/j.ejca.2011.09.006
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