Document Detail

Time-dependent dephosphorylation through serine/threonine phosphatases is required for stable adhesion of highly and poorly metastatic HT-29 colon carcinoma cell lines to collagen.
MedLine Citation:
PMID:  10953284     Owner:  NLM     Status:  MEDLINE    
Adhesion stabilization is a prerequisite for the long-term adhesion of circulating metastatic tumor cells, and tumor cells with different metastatic potential demonstrate distinct patterns of cell adhesion properties. An important event during formation of organ metastases is integrin-mediated extracellular matrix (ECM) binding that can initiate signal transduction events. Recently we reported that Ser/Thr kinases are involved in regulation of tumor cell adhesion. In the present study the influence of dephosphorylation by Ser/Thr protein phosphatases (PPases) on tumor cell adhesion was investigated. Pretreatment of poorly and highly metastatic human HT-29 colon carcinoma cells with the broad-range inhibitors sodium fluoride (NaF) and sodium pyrophosphate (PyroP) resulted in strong reduction in adhesion of HT-29 cells to various ECM components. Surprisingly, when specific Ser/Thr PPase inhibitors like tautomycin were used we found only a partial reduction in adhesion of highly metastatic HT-29LMM cells to collagen I but not to collagen IV. Other inhibitors did not inhibit adhesion, and poorly metastatic HT-29P were not affected by any specific Ser/Thr PPase inhibitors. Therefore, the effects of NaF on adhesion-mediated Tyr phosphorylation were investigated further. Pretreatment with this inhibitor led to a reduction in phosphorylation of focal adhesion kinase (FAK). In contrast, in cells grown adherent to tissue culture dishes, low concentrations of NaF increased FAK phosphorylation whereas high concentrations inhibited the amount of phosphorylated FAK. Although NaF inhibited adhesions it did not cause changes in cell morphology or detachment of cells from ECM. We hypothesize that dual-specific PPases may be involved in the regulation and establishment of new adhesive interactions in HT-29 cells, but they are not required for maintenance of stable adhesions to ECM.
J Haier; G L Nicolson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  20     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2000 Jul-Aug
Date Detail:
Created Date:  2000-08-31     Completed Date:  2000-08-31     Revised Date:  2012-06-05    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  GREECE    
Other Details:
Languages:  eng     Pagination:  2265-71     Citation Subset:  IM    
Institute for Molecular Medicine, Huntington Beach, CA 92649-1041, USA.
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MeSH Terms
Cell Adhesion
Collagen / physiology*
Colonic Neoplasms / pathology*
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
HT29 Cells
PTEN Phosphohydrolase
Phosphoprotein Phosphatases / physiology*
Phosphoric Monoester Hydrolases / physiology
Protein-Tyrosine Kinases / metabolism
Sodium Fluoride / pharmacology
Time Factors
Tumor Suppressor Proteins*
Tyrosine / metabolism
Reg. No./Substance:
0/Tumor Suppressor Proteins; 55520-40-6/Tyrosine; 7681-49-4/Sodium Fluoride; 9007-34-5/Collagen; EC Adhesion Kinase 1; EC Kinases; EC Adhesion Protein-Tyrosine Kinases; EC protein, human; EC 3.1.3.-/Phosphoric Monoester Hydrolases; EC Phosphatases; EC protein, human; EC Phosphohydrolase

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