Intracellular targets of RGDS peptide in melanoma cells

Maria S. Aguzzi, Paola Fortugno, Claudia Giampietri, Gianluca Ragone, Maurizio C. Capogrossi, Antonio Facchiano

Research output: Contribution to journalArticle

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Abstract

Background: RGD-motif acts as a specific integrins-ligand and regulates a variety of cell-functions via extracellular action affecting cell-adhesion properties. However, increasing evidence identifies additional RGDS-functions at intracellular level. Previous reports show RGDS-internalization in endothelial cells, cardiomyocytes and lymphocytes, indicating intracellular targets such as caspase-8 and caspase-9, and suggest RGDS specific activity at cytoplasmic level. Given the role RGDS-peptides play in controlling proliferation and apoptosis in several cell types, investigating intracellular targets of RGDS in melanoma cells may un-reveal novel molecular targets and key pathways, potentially useful for a more effective approach to melanoma treatment.Results: 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 μM) 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.Conclusions: 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.

Original languageEnglish
Article number84
JournalMolecular Cancer
Volume9
DOIs
Publication statusPublished - Apr 22 2010

Fingerprint

arginyl-glycyl-aspartyl-serine
Melanoma
Caspase 8
RGES peptide
Caspase 9
Immunoprecipitation
Cardiac Myocytes
Cell Adhesion
Integrins
Caspase 3
Adhesives
Small Interfering RNA
Extracellular Matrix
Cell Survival
Cell Cycle
Endothelial Cells
Lymphocytes
Apoptosis
Ligands

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Oncology

Cite this

Aguzzi, M. S., Fortugno, P., Giampietri, C., Ragone, G., Capogrossi, M. C., & Facchiano, A. (2010). Intracellular targets of RGDS peptide in melanoma cells. Molecular Cancer, 9, [84]. https://doi.org/10.1186/1476-4598-9-84

Intracellular targets of RGDS peptide in melanoma cells. / Aguzzi, Maria S.; Fortugno, Paola; Giampietri, Claudia; Ragone, Gianluca; Capogrossi, Maurizio C.; Facchiano, Antonio.

In: Molecular Cancer, Vol. 9, 84, 22.04.2010.

Research output: Contribution to journalArticle

Aguzzi, MS, Fortugno, P, Giampietri, C, Ragone, G, Capogrossi, MC & Facchiano, A 2010, 'Intracellular targets of RGDS peptide in melanoma cells', Molecular Cancer, vol. 9, 84. https://doi.org/10.1186/1476-4598-9-84
Aguzzi MS, Fortugno P, Giampietri C, Ragone G, Capogrossi MC, Facchiano A. Intracellular targets of RGDS peptide in melanoma cells. Molecular Cancer. 2010 Apr 22;9. 84. https://doi.org/10.1186/1476-4598-9-84
Aguzzi, Maria S. ; Fortugno, Paola ; Giampietri, Claudia ; Ragone, Gianluca ; Capogrossi, Maurizio C. ; Facchiano, Antonio. / Intracellular targets of RGDS peptide in melanoma cells. In: Molecular Cancer. 2010 ; Vol. 9.
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