The PTEN lipid phosphatase domain is not required to inhibit invasion of glioma cells

The tumor suppressor PTEN negatively controls the phosphoinositide 3-kinase pathway for cell survival by dephosphorylating the phospholipid substrates phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. PTEN has been proposed to dephosphorylate focal adhesion kinase a...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1999-11, Vol.59 (21), p.5479-5482
Main Authors: MAIER, D, JONES, G, XINWEI LI, SCHÖNTHAL, A. H, GRATZL, O, VAN MEIR, E. G, MERLO, A
Format: Article
Language:English
Subjects:
Biological and medical sciences
Brain Neoplasms - metabolism
Cell Adhesion Molecules - metabolism
Cell Movement
DNA, Complementary - metabolism
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Gene Expression Regulation, Neoplastic
Glioma - metabolism
Humans
Immunohistochemistry
Medical sciences
Mutation
Neoplasm Invasiveness
Neurology
Phenotype
Phosphoric Monoester Hydrolases - metabolism
Phosphorylation
Protein-Tyrosine Kinases - metabolism
PTEN Phosphohydrolase
Signal Transduction
Transfection
Tumor Cells, Cultured
Tumor Suppressor Proteins
Tumors of the nervous system. Phacomatoses
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Summary:The tumor suppressor PTEN negatively controls the phosphoinositide 3-kinase pathway for cell survival by dephosphorylating the phospholipid substrates phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. PTEN has been proposed to dephosphorylate focal adhesion kinase and is implicated in the regulation of cell spreading and motility. We analyzed the role of PTEN in invasion using the two highly infiltrative glioma cell lines U87MG (which lacks functional PTEN) and LN229 (wild-type PTEN). After constitutive overexpression of wild-type and phosphatase-deficient (C124S) PTEN, we found significant inhibition of invasion (50-70%) independent of the PTEN status of the cell and of the catalytic core domain of PTEN. Although wild-type but not mutant (C124S) PTEN decreased PKB/Akt phosphorylation and induced a stellate morphology in U87MG cells, an accompanying reduction of focal adhesion kinase phosphorylation was not seen. We conclude that phosphatase-independent domains of PTEN markedly reduced the invasive potential of glioma cells, defining a structural role for PTEN that regulates cell motility distinct of the PKB/Akt pathway.
ISSN:0008-5472
1538-7445