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[Cancer Research 59, 5479-5482, November 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 5479-5482, November 1, 1999]
© 1999 American Association for Cancer Research

Advances in Brief

The PTEN Lipid Phosphatase Domain Is Not Required to Inhibit Invasion of Glioma Cells1

Daniel Maier, Graham Jones, Xinwei Li, Axel H. Schönthal, Otmar Gratzl, Erwin G. Van Meir and Adrian Merlo2

Laboratory of Molecular Neuro-Oncology, Departments of Research and Neurosurgery, University of CH-4031 Basel, Switzerland [D. M., G. J., O. G., A. M.]; Laboratory of Molecular Neuro-Oncology, Department of Neurological Surgery and Winship Cancer Center, Emory University, Atlanta, Georgia 30322 [E. G.V. M.]; and Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, California 90033 [X. L., A. H. S.]

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.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.