Loss of PTEN binding adapter protein NHERF1 from plasma membrane in glioblastoma contributes to PTEN inactivation.

ABSTRACT: Glioblastoma multiforme (GBM) is a severe brain malignancy with limited treatment and dismal prognosis. The tumor suppressor PTEN, a major inhibitor of the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway, is frequently deleted in GBM tumors. PTEN antagonizes PI3K by dephosphorylating PI3K phosphoinositide substrates at the plasma membrane. The PTEN binding adapter protein NHERF1/EBP50 is overexpressed in GBM but its effects on tumorigenesis have yet to be determined. Here, we show that NHERF1 is localized to the plasma membrane in normal astrocytes and to the cytoplasm of GBM tumor cells. This cytoplasmic shift paralleled an altered membrane distribution of wild-type PTEN with consecutive Akt activation. Membrane re-targeting of NHERF1 in GBM cells recruited PTEN to the membrane and su

SUBMITTER: Molina JR 

PROVIDER: S-EPMC2932801 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature