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N-cadherin expression level modulates integrin-mediated polarity and strongly impacts on the speed and directionality of glial cell migration

Emeline Camand 1 Florent Peglion 2 Naël Osmani 3 Marc Sanson 4 Sandrine Etienne-Manneville 2, * 
* Corresponding author
4 INSERM UMR_S975
Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
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.
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Submitted on : Tuesday, January 11, 2022 - 4:26:40 PM
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Emeline Camand, Florent Peglion, Naël Osmani, Marc Sanson, Sandrine Etienne-Manneville. N-cadherin expression level modulates integrin-mediated polarity and strongly impacts on the speed and directionality of glial cell migration. Journal of Cell Science, 2012, 125 (4), pp.844-857. ⟨10.1242/jcs.087668⟩. ⟨pasteur-03521577⟩

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