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Heparin plays a key regulatory role via a p53/FAK‐dependent signaling in melanoma cell adhesion and migration
Author(s) -
Chalkiadaki Georgia,
Nikitovic Dragana,
Berdiaki Aikaterini,
Katonis Pavlos,
Karamanos Nikos K.,
Tzanakakis George N.
Publication year - 2011
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.421
Subject(s) - microbiology and biotechnology , heparin , key (lock) , chemistry , cell adhesion , signal transduction , cancer research , cell , biochemistry , biology , ecology
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