Document Detail

The p53/p21Cip1/ Waf1 pathway mediates the effects of SPARC on melanoma cell cycle progression.
MedLine Citation:
PMID:  20955243     Owner:  NLM     Status:  In-Process    
Secreted protein acidic and rich in cysteine (SPARC), or osteonectin, belongs to the family of matricellular proteins that modulate cell-matrix interactions and cellular functions. SPARC is highly expressed in melanoma, and we reported that SPARC promotes epithelial/mesenchymal-like changes and cell migration. Here, we used siRNA and conditional shRNA to investigate the contribution of tumor-derived SPARC to melanoma cell growth in vitro and in vivo. We found that depletion of SPARC induces G2/M cell cycle arrest and tumor growth inhibition with activation of p53 and induction of p21(Cip1/Waf1) acting as a checkpoint, preventing efficient mitotic progression. In addition, we demonstrate that reduced mesenchymal features and the invasive potential of SPARC-silenced cells are independent of p21(Cip1/Waf1) induction and cell cycle arrest. Importantly, overexpression of SPARC reduces p53 protein levels and leads to an increase in cell number during exponential growth. Our findings indicate that in addition to its well-known function as a mediator of melanoma cell migration and tumor-host interactions, SPARC regulates, in a cell-autonomous manner, cell cycle progression and proliferation through the p53/p21(Cip1/Waf1) pathway.
Nina Fenouille; Guillaume Robert; Mélanie Tichet; Alexandre Puissant; Maeva Dufies; Stéphane Rocchi; Jean-Paul Ortonne; Marcel Deckert; Robert Ballotti; Sophie Tartare-Deckert
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-17
Journal Detail:
Title:  Pigment cell & melanoma research     Volume:  24     ISSN:  1755-148X     ISO Abbreviation:  Pigment Cell Melanoma Res     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101318927     Medline TA:  Pigment Cell Melanoma Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  219-32     Citation Subset:  IM    
Copyright Information:
© 2010 John Wiley & Sons A/S.
INSERM, U895, University of Nice-Sophia Antipolis, Nice, France.
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