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

Abstract

SummaryPerturbation 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.

Par3 controls neural crest migration by promoting microtubule catastrophe during contact inhibition of locomotion

“…Development (2013) ( Camand et al, 2012;Chausovsky et al, 2000;Dupin et al, 2009). Our analysis of cell adhesion molecules and cell sorting does not support the notion that Par3 regulates cell adhesion in NC cells, as has been shown for other cell types (Xue et al, 2013); however, we cannot rule out the possibility that subtle changes in cell adhesion, undetected in our assays, are modulated by Par3 in NC cells.…”

N-Cadherin Promotes Recruitment and Migration of Neural Progenitor Cells from the SVZ Neural Stem Cell Niche into Demyelinated Lesions

“…A similar characterization using CBR-N-cadherin and JM-N-cadherin encoding retrovirus demonstrated decreased expression of ␤-catenin and p120, respectively (data not shown). In several cell types, cadherins have been found to mediate the cell migration cycle by regulating the placement of focal adhesions to the leading edge of migratory cells (Nelson et al, 2004;Camand et al, 2012). Both talin 1 and vinculin, intricately involved in the formation of focal adhesions, were found to be upregulated at 12 weeks of cuprizone treatment, during which high levels of pEGFR were detected (Table 2; Fig.…”

“…Such signals have been shown to alter the migratory paths of progenitors, redirecting them toward areas of brain damage (Cayre et al, 2009). In particular, EGFR signaling has proven to be crucial in promoting NPC proliferation, migration, and recruitment during development and in pathological conditions (Aguirre and Gallo, 2007;Aguirre et al, 2007;Gonzalez-Perez et al, 2009).…”

Molecular Mechanisms of Glioma Cell Motility

“…Glioma cells with high E-cadherin expression show greater invasion when orthotopically implanted in mice (176). In contrast to its role in carcinoma, N-cadherin is frequently downregulated in GBM compared to the healthy brain (177,178). N-cadherin overexpression has been shown to decrease glioma invasion in vitro and in vivo (179).…”