A cadherin switch underlies malignancy in high-grade gliomas

Although the infiltrative behavior of malignant gliomas is one of their most critical aspects, the mechanisms underlying it have not yet been elucidated. To migrate in the brain parenchyma, malignant glioma cells need to bypass the cell-cell contact inhibitory signals. Here we propose that the blinding of cell-cell contact sensing in gliomas is caused by an unusual mechanism of cadherin switch, involving the replacement of N-cadherin with R-cadherin (Rcad) at the cell-cell junctions and the activation of ERK and p27. In our model of malignant glioma, we found that Rcad expression is necessary and sufficient to release cells from contact inhibition of proliferation, and is necessary, although not sufficient, for overriding contact inhibition of migration and for tumorigenicity. Altogether, these observations suggest that Rcad is a potential target for malignant glioma therapies.