PTEN regulates tumor cell adhesion of colon carcinoma cells under dynamic conditions of fluid flow
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PTEN regulates tumor cell adhesion of colon carcinoma cells under dynamic conditions of fluid flow. / Haier, Jörg; Nicolson, Garth L.
In: ONCOGENE, Vol. 21, No. 9, 21.02.2002, p. 1450-60.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - PTEN regulates tumor cell adhesion of colon carcinoma cells under dynamic conditions of fluid flow
AU - Haier, Jörg
AU - Nicolson, Garth L
PY - 2002/2/21
Y1 - 2002/2/21
N2 - The regulation of integrin-mediated cell adhesion and its stabilization involves different phosphorylation and dephosphorylation events. Focal adhesion kinase (FAK) has been recently found to be a substrate of the dual-specific phosphatase PTEN in glioma cells, where it appears to be involved in regulation of cell spreading and migration as part of focal adhesions. We have investigated the role of PTEN in cell adhesion of HT-29 human colon carcinoma cells under static and hydrodynamic conditions of fluid flow. PTEN coprecipitated with FAK and paxillin dependent on the formation of adhesions to collagens. This corresponded with an adhesion-dependent increase in Tyr-phosphatase activity of PTEN. Using preparations of native FAK and PTEN from HT-29 cells in a specific Tyr-phosphatase assay FAK was identified as substrate for this dephosphorylation. If expression of PTEN was reduced using antisense oligonucleotides cell adhesion under dynamic conditions of laminar flow, but not under static conditions was significantly increased. In addition, cell spreading was increased in cells with reduced PTEN expression. We conclude that PTEN appears to be involved in the regulation of integrin-mediated adhesion through dephosphorylation of FAK. This phosphatase might play a role as a negative regulator for the formation of stable HT-29 cell adhesion to extracellular matrix.
AB - The regulation of integrin-mediated cell adhesion and its stabilization involves different phosphorylation and dephosphorylation events. Focal adhesion kinase (FAK) has been recently found to be a substrate of the dual-specific phosphatase PTEN in glioma cells, where it appears to be involved in regulation of cell spreading and migration as part of focal adhesions. We have investigated the role of PTEN in cell adhesion of HT-29 human colon carcinoma cells under static and hydrodynamic conditions of fluid flow. PTEN coprecipitated with FAK and paxillin dependent on the formation of adhesions to collagens. This corresponded with an adhesion-dependent increase in Tyr-phosphatase activity of PTEN. Using preparations of native FAK and PTEN from HT-29 cells in a specific Tyr-phosphatase assay FAK was identified as substrate for this dephosphorylation. If expression of PTEN was reduced using antisense oligonucleotides cell adhesion under dynamic conditions of laminar flow, but not under static conditions was significantly increased. In addition, cell spreading was increased in cells with reduced PTEN expression. We conclude that PTEN appears to be involved in the regulation of integrin-mediated adhesion through dephosphorylation of FAK. This phosphatase might play a role as a negative regulator for the formation of stable HT-29 cell adhesion to extracellular matrix.
KW - Arsenicals
KW - Blotting, Western
KW - Cell Adhesion
KW - Cell Size
KW - Collagen
KW - Colonic Neoplasms
KW - Cytoskeletal Proteins
KW - Dose-Response Relationship, Drug
KW - Enzyme Activation
KW - Focal Adhesion Kinase 1
KW - Focal Adhesion Protein-Tyrosine Kinases
KW - Humans
KW - Oligonucleotides, Antisense
KW - PTEN Phosphohydrolase
KW - Paxillin
KW - Phosphoproteins
KW - Phosphoric Monoester Hydrolases
KW - Phosphorylation
KW - Phosphotyrosine
KW - Protein Binding
KW - Protein-Tyrosine Kinases
KW - Rheology
KW - Stress, Mechanical
KW - Tumor Cells, Cultured
KW - Tumor Suppressor Proteins
U2 - 10.1038/sj.onc.1205213
DO - 10.1038/sj.onc.1205213
M3 - SCORING: Journal article
C2 - 11857088
VL - 21
SP - 1450
EP - 1460
JO - ONCOGENE
JF - ONCOGENE
SN - 0950-9232
IS - 9
ER -