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Guerrico AMG , Jaffer ZM , Page RE , Braunewell KH , Chernoff J , Klein-Szanto AJP
Visinin-like protein-1 is a potent inhibitor of cell adhesion and migration in squamous carcinoma cells
Oncogene. 2005 Mar 31;24(14) :2307-2316
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Abstract
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 downregulating alpha v and alpha 5 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 increas ed adhesion to fibro-nectin and enhanced expression of av and %5 integrin subunits together with increased cell migration. Function-blocking assays with inhibitory anti-alpha 5 and anti-alpha v 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.
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English Article