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Heparin plays a key regulatory role via a p53/FAK-dependent signaling in melanoma cell adhesion and migration.
MedLine Citation:
PMID:  21360640     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Heparin and its various derivatives affect cancer progression in humans. In this study, we show that heparin uptaken intracellularly by melanoma cells activated a signaling cascade, which in turn inhibited melanoma cell adhesion and migration. The reduced ability of M5 cells to adhere onto the fibronectin (FN) substrate was directly correlated to a decrease in the expression of focal adhesion kinase (FAK), which is a key regulator of melanoma motility. Cell treatment with heparin caused a marked downregulation in FAK expression (P ≤ 0.01). This is followed by an analogous inhibition of both constitutive and FN-induced FAK Y397-phosphorylation (P ≤ 0.01). Moreover, heparin stimulated the p53 expression (P ≤ 0.001) of M5 cells and its increased accumulation in the nucleus. This favors a decrease in FAK promoter activation and explains the reduced FAK transcript and protein levels. In conclusion, the results of this study clearly demonstrate that the action of heparin in the regulation of melanoma cell adhesion and migration involves a p53/FAK/signaling pathway, which may be of importance in molecular targeted therapy of the disease. © 2011 IUBMB IUBMB Life, 63(2): 109-119, 2011.
Authors:
Georgia Chalkiadaki; Dragana Nikitovic; Aikaterini Berdiaki; Pavlos Katonis; Nikos K Karamanos; George N Tzanakakis
Publication Detail:
Type:  Journal Article     Date:  2011-02-24
Journal Detail:
Title:  IUBMB life     Volume:  63     ISSN:  1521-6551     ISO Abbreviation:  IUBMB Life     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-03-01     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100888706     Medline TA:  IUBMB Life     Country:  England    
Other Details:
Languages:  eng     Pagination:  109-19     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley Periodicals, Inc.
Affiliation:
Department of Histology, Medical School, University of Crete, Heraklion 71003, Greece. tzanakak@med.uoc.gr.
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