| Autor: |
Gonzalez Guerrico, Anatilde M., Jaffer, Zahara M., Page, Robert E, Braunewell, Karl-Heinz, Chernoff, Jonathan, Klein-Szanto, Andres J.P. |
| Předmět: |
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| Zdroj: |
Oncogene; 3/31/2005, Vol. 24 Issue 14, p2307-2316, 10p |
| Abstrakt: |
Tumor cell invasion is a highly integrated and complex process comprising several biologically distinct functions such as cell adhesion, motility, proteolysis, etc. Visinin-like protein-1 (VILIP-1), a member of the neuronal EF-hand calcium-sensor protein family, plays a role in regulating tumor cell invasiveness of mouse squamous cell carcinoma (SCC). VILIP-1 enhances cyclic adenosine monophosphate levels through PKA induction. However, the mechanism by which VILIP-1 reduces cell invasiveness is not well understood. In this study, we show that VILIP-1 decreased cell adhesion and migration/invasiveness of highly invasive mouse SCC cells. Forced expression of VILIP-1 reduced cell adhesion to fibronectin in parallel to downregulatingav anda5 integrin subunit levels. VILIP-1 overexpression also led to decreased migration ability. Conversely, short hairpin RNA-mediated VILIP-1 knock-down of SCC cells'characterized by little or no invasiveness, correlated with increased adhesion to fibronectin and enhanced expression ofav anda5 integrin subunits together with increased cell migration. Function-blocking assays with inhibitory anti-a5 and anti-av integrin antibodies showed that both subunits contributed to cell adhesion, migration, and invasiveness of highly invasive SCC cell lines. These results point to a critical role of VILIP-1 in regulating cell adhesion and migration by downregulation of fibronectin receptor expression. Decreased or absent VILIP-1 expression in SCC cell subpopulations may lead to a more advanced malignant phenotype characterized by changes in adhesive ability and increased cell motility, suggestive of a tumor suppressor function.Oncogene (2005) 24, 2307-2316. doi:10.1038/sj.onc.1208476 Published online 14 February 2005 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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