Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN.
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.
Tamura
M
M
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892-4370, USA. mtamura@yoda.nidr.nih.gov
Gu
J
J
Matsumoto
K
K
Aota
S
S
Parsons
R
R
Yamada
K M
KM
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D048429:Cell Size; D003208:Concanavalin A; D015536:Down-Regulation; D004440:Ecdysone / Q000494:pharmacology; D005353:Fibronectins; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016147:Genes, Tumor Suppressor; D006801:Humans; D016023:Integrins / Q000502:physiology; D051379:Mice; D009154:Mutation; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases; D010766:Phosphorylation; D011107:Polylysine; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D016023:Integrins; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D003208:Concanavalin A; D011107:Polylysine; D004440:Ecdysone; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; D010744:Phosphoric Monoester Hydrolases; D017027:Protein Tyrosine Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human