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Science 5 June 1998:
Vol. 280. no. 5369, pp. 1614 - 1617
DOI: 10.1126/science.280.5369.1614
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Reports

Inhibition of Cell Migration, Spreading, and Focal Adhesions by Tumor Suppressor PTEN

Masahito Tamura, * Jianguo Gu, Kazue Matsumoto, Shin-ichi Aota, Ramon Parsons, Kenneth M. Yamada *

The tumor suppressor PTEN is a phosphatase with sequence similarity to the cytoskeletal protein tensin. Here the cellular roles of PTEN were investigated. Overexpression of PTEN inhibited cell migration, whereas antisense PTEN enhanced migration. Integrin-mediated cell spreading and the formation of focal adhesions were down-regulated by wild-type PTEN but not by PTEN with an inactive phosphatase domain. PTEN interacted with the focal adhesion kinase FAK and reduced its tyrosine phosphorylation. Overexpression of FAK partially antagonized the effects of PTEN. Thus, PTEN phosphatase may function as a tumor suppressor by negatively regulating cell interactions with the extracellular matrix.

M. Tamura, J. Gu, K. Matsumoto, S. Aota, K. M. Yamada, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental Research, National Institutes of Health, Building 30, Room 421, 30 Convent Drive MSC 4370, Bethesda, MD 20892-4370, USA.
R. Parsons, Departments of Pathology and Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
M. Tamura, J. Gu, K. Matsumoto, S. Aota, K. M. Yamada, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental Research, National Institutes of Health, Building 30, Room 421, 30 Convent Drive MSC 4370, Bethesda, MD 20892-4370, USA.
R. Parsons, Departments of Pathology and Medicine, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
*   To whom correspondence should be addressed. E-mail: mtamura{at}yoda.nidr.nih.gov or kyamada{at}yoda.nidr.nih.gov

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   Abstract »    Full Text »    PDF »
Integration of Cell Attachment, Cytoskeletal Localization, and Signaling by Integrin-linked Kinase (ILK), CH-ILKBP, and the Tumor Suppressor PTEN.
S. Attwell, J. Mills, A. Troussard, C. Wu, and S. Dedhar (2003)
Mol. Biol. Cell 14, 4813-4825
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{beta}1 Integrin/Focal Adhesion Kinase-mediated Signaling Induces Intercellular Adhesion Molecule 1 and Receptor Activator of Nuclear Factor {kappa}B Ligand on Osteoblasts and Osteoclast Maturation.
S. Nakayamada, Y. Okada, K. Saito, M. Tamura, and Y. Tanaka (2003)
J. Biol. Chem. 278, 45368-45374
   Abstract »    Full Text »    PDF »
Matrix Metalloproteinase 19 Regulates Insulin-like Growth Factor-mediated Proliferation, Migration, and Adhesion in Human Keratinocytes through Proteolysis of Insulin-like Growth Factor Binding Protein-3.
T. Sadowski, S. Dietrich, F. Koschinsky, and R. Sedlacek (2003)
Mol. Biol. Cell 14, 4569-4580
   Abstract »    Full Text »    PDF »
PTEN: tumour suppressor, multifunctional growth regulator and more.
D. C.I. Goberdhan and C. Wilson (2003)
Hum. Mol. Genet. 12, R239-248
   Abstract »    Full Text »    PDF »
Src Family Protein-tyrosine Kinases Alter the Function of PTEN to Regulate Phosphatidylinositol 3-Kinase/AKT Cascades.
Y. Lu, Q. Yu, J. H. Liu, J. Zhang, H. Wang, D. Koul, J. S. McMurray, X. Fang, W.K. A. Yung, K. A. Siminovitch, et al. (2003)
J. Biol. Chem. 278, 40057-40066
   Abstract »    Full Text »    PDF »
Targeting Membrane-localized Focal Adhesion Kinase to Focal Adhesions: ROLES OF TYROSINE PHOSPHORYLATION AND SRC FAMILY KINASES.
B.-Z. Katz, L. Romer, S. Miyamoto, T. Volberg, K. Matsumoto, E. Cukierman, B. Geiger, and K. M. Yamada (2003)
J. Biol. Chem. 278, 29115-29120
   Abstract »    Full Text »    PDF »
Tyrosine phosphorylation of the CrkII adaptor protein modulates cell migration.
T. Takino, M. Tamura, H. Miyamori, M. Araki, K. Matsumoto, H. Sato, and K. M. Yamada (2003)
J. Cell Sci. 116, 3145-3155
   Abstract »    Full Text »    PDF »
Protein tyrosine phosphatase RQ is a phosphatidylinositol phosphatase that can regulate cell survival and proliferation.
A. Oganesian, M. Poot, G. Daum, S. A. Coats, M. B. Wright, R. A. Seifert, and D. F. Bowen-Pope (2003)
PNAS 100, 7563-7568
   Abstract »    Full Text »    PDF »
Antiangiogenic Effect of KR-31372 by Apoptosis via Mediation of Mitochondrial KATP Channel Opening and the Phosphatase and Tensin Homolog Deleted from Chromosome 10 Phosphorylation.
K. Y. Kim, Y. W. Shin, S.-O. Kim, H. Lim, S.-E. Yoo, and K. W. Hong (2003)
J. Pharmacol. Exp. Ther. 305, 1142-1149
   Abstract »    Full Text »    PDF »
Histone H1.2 is a substrate for denitrase, an activity that reduces nitrotyrosine immunoreactivity in proteins.
Y. Irie, M. Saeki, Y. Kamisaki, E. Martin, and F. Murad (2003)
PNAS 100, 5634-5639
   Abstract »    Full Text »    PDF »
Anti-angiogenic Activity of the Recombinant Kringle Domain of Urokinase and Its Specific Entry into Endothelial Cells.
K. S. Kim, Y.-K. Hong, Y. A. Joe, Y. Lee, J.-Y. Shin, H.-E. Park, I.-H. Lee, S.-Y. Lee, D.-K. Kang, S.-I. Chang, et al. (2003)
J. Biol. Chem. 278, 11449-11456
   Abstract »    Full Text »    PDF »
BMP2 exposure results in decreased PTEN protein degradation and increased PTEN levels.
K. A. Waite and C. Eng (2003)
Hum. Mol. Genet. 12, 679-684
   Abstract »    Full Text »    PDF »
Growth and Molecular Profile of Lung Cancer Cells Expressing Ectopic LKB1: Down-Regulation of the Phosphatidylinositol 3'-Phosphate Kinase/PTEN Pathway.
A. I. Jimenez, P. Fernandez, O. Dominguez, A. Dopazo, and M. Sanchez-Cespedes (2003)
Cancer Res. 63, 1382-1388
   Abstract »    Full Text »    PDF »
PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum.
S. Marino, P. Krimpenfort, C. Leung, H. A. G. M. van der Korput, J. Trapman, I. Camenisch, A. Berns, and S. Brandner (2003)
Development 129, 3513-3522
   Abstract »    Full Text »    PDF »
Differential Role of Proline-Rich Tyrosine Kinase 2 and Focal Adhesion Kinase in Determining Glioblastoma Migration and Proliferation.
C. A. Lipinski, N. L. Tran, C. Bay, J. Kloss, W. S. McDonough, C. Beaudry, M. E. Berens, and J. C. Loftus (2003)
Mol. Cancer Res. 1, 323-332
   Abstract »    Full Text »    PDF »
PTEN Regulates RANKL- and Osteopontin-stimulated Signal Transduction during Osteoclast Differentiation and Cell Motility.
T. Sugatani, U. Alvarez, and K. A. Hruska (2003)
J. Biol. Chem. 278, 5001-5008
   Abstract »    Full Text »    PDF »
Increased Nuclear Phosphatase and Tensin Homologue Deleted on Chromosome 10 Is Associated with G0-G1 in MCF-7 Cells.
M. E. Ginn-Pease and C. Eng (2003)
Cancer Res. 63, 282-286
   Abstract »    Full Text »    PDF »
PTP{alpha} regulates integrin-stimulated FAK autophosphorylation and cytoskeletal rearrangement in cell spreading and migration.
L. Zeng, X. Si, W.-P. Yu, H. T. Le, K. P. Ng, R. M.H. Teng, K. Ryan, D. Z.-M. Wang, S. Ponniah, and C. J. Pallen (2003)
J. Cell Biol. 160, 137-146
   Abstract »    Full Text »    PDF »
PTEN Suppresses Hyaluronic Acid-induced Matrix Metalloproteinase-9 Expression in U87MG Glioblastoma Cells through Focal Adhesion Kinase Dephosphorylation.
M.-J. Park, M.-S. Kim, I.-C. Park, H.-S. Kang, H. Yoo, S. H. Park, C. H. Rhee, S.-I. Hong, and S.-H. Lee (2002)
Cancer Res. 62, 6318-6322
   Abstract »    Full Text »    PDF »
Low Mr Phosphotyrosine Protein Phosphatase Associates and Dephosphorylates p125 Focal Adhesion Kinase, Interfering with Cell Motility and Spreading.
S. Rigacci, E. Rovida, P. D. Sbarba, and A. Berti (2002)
J. Biol. Chem. 277, 41631-41636
   Abstract »    Full Text »    PDF »
PTEN Associates with the Vault Particles in HeLa Cells.
Z. Yu, N. Fotouhi-Ardakani, L. Wu, M. Maoui, S. Wang, D. Banville, and S.-H. Shen (2002)
J. Biol. Chem. 277, 40247-40252
   Abstract »    Full Text »    PDF »
Requirement of Phosphoinositide 3-Kinase and Akt for Interferon-beta -mediated Induction of the beta -R1 (SCYB11) Gene.
M. R. S. Rani, L. Hibbert, N. Sizemore, G. R. Stark, and R. M. Ransohoff (2002)
J. Biol. Chem. 277, 38456-38461
   Abstract »    Full Text »    PDF »
Role of alpha vbeta 3-integrin in TNF-alpha -induced endothelial cell migration.
B. Gao, T. M. Saba, and M.-F. Tsan (2002)
Am J Physiol Cell Physiol 283, C1196-C1205
   Abstract »    Full Text »    PDF »


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