A cadherin switch underlies malignancy in high-grade gliomas
A cadherin switch underlies malignancy in high-grade gliomas
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DOI：
10.1038/onc.2014.122
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发表时间：
2015-04-09
期刊：
影响因子：
8
通讯作者：
Malatesta, P.
中科院分区：
文献类型：
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作者：
Appolloni, I.;Barilari, M.;Malatesta, P.
虽然恶性胶质瘤的浸润行为是其最重要的方面之一，但其机制尚未阐明。恶性胶质瘤细胞要在脑实质中迁移，需要绕过细胞-细胞接触抑制信号。在这里，我们提出，致盲的细胞间接触感应胶质瘤是由一个不寻常的机制，钙粘蛋白开关，涉及更换N-钙粘蛋白与R-钙粘蛋白（Rcad）在细胞间连接和ERK和p27的激活。在我们的恶性胶质瘤模型中，我们发现Rcad表达是必要的，足以释放细胞的接触抑制增殖，是必要的，虽然不是足够的，压倒接触抑制迁移和致瘤性。总之，这些观察结果表明，Rcad是恶性胶质瘤治疗的潜在靶点。
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.