Advertisement

Der Tumorsuppressor PTEN reguliert metastatische Tumorzelladhäsion bei Kolonkarzinomzellen

  • J. Haier
  • N. Senninger
  • G. L. Nicolson
Conference paper
Part of the Deutsche Gesellschaft für Chirurgie book series (DTGESCHIR, volume 31)

Abstract

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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Haier J, Nicolson GL (2000) Tumor cell adhesion of human colon carcinoma cells with different metastatic properties to extracellular matrix under dynamic conditions of laminar flow. J Cancer Res Clin Oncol 126:699–706PubMedCrossRefGoogle Scholar
  2. 2.
    Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers LL, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R (1997) PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast and prostate cancer. Science 275: 1943 - 1947PubMedCrossRefGoogle Scholar
  3. 3.
    Gu J, Tamura M, Yamada KM (1998) Tumor suppressor PTEN inhibits integrin- and growth factor-mediated mitogen-activated protein (MAP) kinase signaling pathway. J Cell Biol 143: 1375– 1383PubMedCrossRefGoogle Scholar
  4. 4.
    Tamura M, Gu J, Danen EH, Takino T, Miyamoto S, Yamada KM (1999) PTEN interactions with focal adhesion kinase and suppression of the extracellular matrix-dependent phosphatidylinositol 3-kinase/ Akt cellsurvival pathway. J Biol Chem 274: 20693 - 20703PubMedCrossRefGoogle Scholar
  5. 5.
    Haier J, Nasralla M, Nicolson GL (1999) ß1-integrin mediated dynamic adhesion of colon carcinoma cells to extracellular matrix under laminar flow. Clin Exp Metastasis 17: 377–388PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • J. Haier
    • 1
    • 2
    • 3
  • N. Senninger
    • 1
  • G. L. Nicolson
    • 2
  1. 1.Molekularbiologisches Labor, Klinik für AllgemeinchirurgieUniversitätsklinikum MünsterGermany
  2. 2.Institute for Molecular MedicineHuntington BeachUSA
  3. 3.Molekularbiologisches Labor, Klinik und Poliklinik für Allgemeine ChirurgieUniversitätsklinik Freiburg i. Br.MünsterGermany

Personalised recommendations