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  • Original Paper
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Visinin-like protein-1 is a potent inhibitor of cell adhesion and migration in squamous carcinoma cells

Oncogene volume 24, pages 2307–2316 (2005)Cite this article

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 αv and α5 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 of αv and α5 integrin subunits together with increased cell migration. Function-blocking assays with inhibitory anti-α5 and anti-αv 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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Abbreviations

VILIP-1:

visinin like protein-1

cAMP:

cyclic adenosine monophosphate

ECM:

extracellular matrix

SCC:

squamous cell carcinoma

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Acknowledgements

This work was supported in part by a grant from the National Institutes of Health CA06927 and by an appropriation from the Commonwealth of Pennsylvania.

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Author notes

  1. Anatilde M Gonzalez Guerrico

    Present address: University of Pennsylvania School of Medicine, Center for Experimental Therapeutics, Philadelphia, PA, 19104, USA

Authors and Affiliations

  1. Department of Pathology, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA

    Anatilde M Gonzalez Guerrico, Robert E Page & Andres JP Klein-Szanto

  2. Tumor Cell Biology Program, Fox Chase Cancer Center, Philadelphia, PA, 19111, USA

    Zahara M Jaffer, Jonathan Chernoff & Andres JP Klein-Szanto

  3. Neuroscience Research Center of the Charité, Humboldt University, Faculty of Medicine, 10117, Berlin, Germany

    Karl-Heinz Braunewell

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  1. Anatilde M Gonzalez Guerrico
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Correspondence to Andres JP Klein-Szanto.

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Gonzalez Guerrico, A., Jaffer, Z., Page, R. et al. Visinin-like protein-1 is a potent inhibitor of cell adhesion and migration in squamous carcinoma cells. Oncogene 24, 2307–2316 (2005). https://doi.org/10.1038/sj.onc.1208476

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