Snail blocks the cell cycle and confers resistance to cell death
Snail blocks the cell cycle and confers resistance to cell death
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DOI：
10.1101/gad.294104
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发表时间：
2004-05-15
影响因子：
10.5
通讯作者：
Nieto, MA
中科院分区：
文献类型：
--
作者：
Vega, S;Morales, AV;Nieto, MA
蜗牛锌指转录因子触发上皮-间质转化（EMTs），赋予上皮细胞在胚胎发育和肿瘤进展过程中的迁移和侵袭特性。在EMT过程中，Snail会引起上皮标记物的丢失，以及细胞形状和间充质标记物表达的改变。在这里，我们发现除了诱导显著的表型改变外，蜗牛还能减弱细胞周期，并赋予抵抗由生存因子的退出和促凋亡信号诱导的细胞死亡的能力。因此，Snail倾向于改变细胞形状而不是细胞分裂，这表明在肿瘤发生方面，尽管增殖的失调/增加对肿瘤的形成和生长至关重要，但对于肿瘤的恶性化可能并非如此。最后，蜗牛对细胞死亡的抵抗为胚胎细胞迁移和殖民遥远的领土提供了选择优势，并为恶性细胞从原发肿瘤中分离、入侵和形成转移提供了选择优势。
The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the expression of mesenchymal markers. Here, we show that in addition to inducing dramatic phenotypic alterations, Snail attenuates the cell cycle and confers resistance to cell death induced by the withdrawal of survival factors and by pro-apoptotic signals. Hence, Snail favors changes in cell shape versus cell division, indicating that with respect to oncogenesis, although a deregulation/increase in proliferation is crucial for tumor formation and growth, this may not be so for tumor malignization. Finally, the resistance to cell death conferred by Snail provides a selective advantage to embryonic cells to migrate and colonize distant territories, and to malignant cells to separate from the primary tumor, invade, and form metastasis.