title: N-cadherin expression level modulates integrin-mediated polarity and strongly impacts on the speed and directionality of glial cell migration.
abstract: Perturbation of cell polarity is a hallmark of cancer cells. In carcinomas, loss of epithelial E-cadherin contributes to the loss of cell polarity and promotes epithelial-mesenchymal transition and carcinoma infiltration. However, the contribution of classical cadherins to the development of non-epithelial tumours is less well documented. We investigated the impact of the level of N-cadherin expression on the polarity and migration of normal and tumour glial cells. Low levels of N-cadherin were frequently observed in human glioma samples and purified glioma cells. Using a wound-healing assay, we show that a decreased level of N-cadherin promotes a faster and less-directed migration both in normal and tumour cells. N-cadherin-mediated contacts control cell velocity and polarity through the regulation of focal adhesions. In cells expressing low levels of N-cadherin, small focal adhesions are present at the entire cell periphery of confluent cells and are not affected by wounding of the cell monolayer. Under these conditions, wound-induced integrin-mediated recruitment of the small GTPase Cdc42, activation of the Cdc42-mediated polarity pathway and centrosome reorientation do not occur. Re-expression of N-cadherin in gliomas restores cell polarity and strongly reduces cell velocity, suggesting that loss of N-cadherin could contribute to the invasive capacity of tumour astrocytes.
authors.affiliation: Institut Pasteur-CNRS URA 2582, Cell Polarity, Migration and Cancer Unit, 25 rue du Dr Roux, 75724 Paris CEDEX 15,  France.
authors.forename: Emeline
authors.initials: E
authors.lastname: Camand
authors.forename: Florent
authors.initials: F
authors.lastname: Peglion
authors.forename: Naël
authors.initials: N
authors.lastname: Osmani
authors.forename: Marc
authors.initials: M
authors.lastname: Sanson
authors.forename: Sandrine
authors.initials: S
authors.lastname: Etienne-Manneville
mesh_terms: D001253:Astrocytes / Q000166:cytology*; D015820:Cadherins / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D016764:Cell Polarity / Q000502:physiology*; D015536:Down-Regulation; D022001:Focal Adhesions; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D064067:Rho Guanine Nucleotide Exchange Factors; D013997:Time Factors; D014945:Wound Healing; D014947:Wounds and Injuries / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; D020662:Guanine Nucleotide Exchange Factors; D016023:Integrins; D064067:Rho Guanine Nucleotide Exchange Factors; D019000:Phosphotyrosine; D016392:Proto-Oncogene Proteins pp60(c-src); D020764:cdc42 GTP-Binding Protein