Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis
Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis
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DOI：
10.1016/j.cell.2004.06.006
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发表时间：
2004-06-25
期刊：
影响因子：
64.5
通讯作者：
Weinberg, RA
中科院分区：
文献类型：
--
作者：
Yang, J;Mani, SA;Weinberg, RA
转移是一个多步骤的过程，在此过程中，癌细胞从原发性肿瘤部位扩散并在远处器官中建立继发性肿瘤。在小鼠乳腺肿瘤模型中寻找转移的关键调节因子时，我们发现转录因子Twist是胚胎形态发生的主要调节因子，在转移中起着至关重要的作用。在高转移性乳腺癌细胞中抑制Twist表达特异性地抑制其从乳腺转移到肺的能力。Twist的异位表达导致E-钙粘蛋白介导的细胞-细胞粘附的丧失、间充质标志物的活化和细胞运动的诱导，表明Twist通过促进上皮-间充质转化（EMT）而有助于转移。在人乳腺癌中，高水平的Twist表达与浸润性小叶癌相关，浸润性小叶癌是一种与E-钙粘蛋白表达缺失相关的高度浸润性肿瘤类型。这些结果建立了Twist、EMT和肿瘤转移之间的机制联系。
Metastasis is a multistep process during which cancer cells disseminate from the site of primary tumors and establish secondary tumors in distant organs. In a search for key regulators of metastasis in a murine breast tumor model, we have found that the transcription factor Twist, a master regulator of embryonic morphogenesis, plays an essential role in metastasis. Suppression of Twist expression in highly metastatic mammary carcinoma cells specifically inhibits their ability to metastasize from the mammary gland to the lung. Ectopic expression of Twist results in loss of E-cadherin-mediated cell-cell adhesion, activation of mesenchymal markers, and induction of cell motility, suggesting that Twist contributes to metastasis by promoting an epithelial-mesenchymal transition (EMT). In human breast cancers, high level of Twist expression is correlated with invasive lobular carcinoma, a highly infiltrating tumor type associated with loss of E-cadherin expression. These results establish a mechanistic link between Twist, EMT, and tumor metastasis.