%0 Journal Article
%T Intracellular targets of RGDS peptide in melanoma cells
%A Maria Aguzzi
%A Paola Fortugno
%A Claudia Giampietri
%A Gianluca Ragone
%A Maurizio C Capogrossi
%A Antonio Facchiano
%J Molecular Cancer
%D 2010
%I BioMed Central
%R 10.1186/1476-4598-9-84
%X In the present study we show for the first time that RGDS-peptide is internalized in melanoma cells in a time-dependent way and exerts strong anti-proliferative and pro-apoptotic effects independently from its extracellular anti-adhesive action. RGES control-peptide did not show biological effects, as expected; nevertheless it is internalized, although with slower kinetics. Survivin, a known cell-cycle and survival-regulator is highly expressed in melanoma cells. Co-immunoprecipitation assays in cell lysates and overlay assays with the purified proteins showed that RGDS interacts with survivin, as well as with procaspase-3, -8 and -9. RGDS-peptide binding to survivin was found to be specific, at high affinity (Kd 27.5 ¦ÌM) and located at the survivin C-terminus. RGDS-survivin interaction appeared to play a key role, since RGDS lost its anti-mitogenic effect in survivin-deprived cells with a specific siRNA.RGDS inhibits melanoma growth with an adhesion-independent mechanism; it is internalized in melanoma cells and specifically interacts with survivin. The present data may indicate a novel role of RGDS-containing peptides physiologically released from the extracellular matrix and may suggest a possible novel anti-proliferation strategy in melanoma.RGD (Arg-Gly-Asp) motif is largely investigated as mediator of cell adhesion to extracellular matrix and to cells, via cell-surface receptors named integrins. These receptors belong to a large family of twenty-four heterodimeric members. Several integrins, including ¦Áv¦Â3, ¦Á5¦Â1, ¦Áv¦Â5, ¦Áv¦Â6 and ¦ÁIIb¦Â3, recognize the RGD motif present in various ECM proteins such as fibronectin, vitronectin, laminin, fibrinogen, von Willebrand factor, osteopontin, thrombospondin, and collagen [1] as well as in disintegrins; others including ¦Á1¦Â1, ¦Á2¦Â1, ¦Á10¦Â1, and ¦Á11¦Â1, interact with the matrix in a RGD-independent manner [2-4]. Integrins activation triggers different signals regulating cell adhesion, migration, survival, apoptosis [1,5,6] as w
%U http://www.molecular-cancer.com/content/9/1/84