PTEN regulates tumor cell adhesion of colon carcinoma cells under dynamic conditions of fluid flow

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 -