The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer
The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer
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DOI：
10.1158/0008-5472.can-07-5682
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发表时间：
2008-01-15
期刊：
影响因子：
11.2
通讯作者：
Brabletz, Thomas
中科院分区：
文献类型：
--
作者：
Spaderna, Simone;Schmalhofer, Otto;Brabletz, Thomas
侵袭和转移是恶性肿瘤进展的标志，也是癌症死亡的主要原因。胚胎计划“上皮-间充质转化”(EMT)被认为通过允许肿瘤细胞扩散而触发侵袭。在这里，我们描述了EMT诱导的转录抑制因子ZEB1促进结直肠癌细胞转移和细胞极性丧失。因此，ZEB1抑制细胞极性因子的表达，特别是Lgl2的表达，我们发现Lgl2在结直肠癌和乳腺癌中减少。我们进一步表明，Lgl2表达的保留对上皮表型至关重要，其丢失可能与转移有关。因此，通过将EMT、极性丧失和转移联系起来，ZEB1是恶性肿瘤进展的关键促进剂。
Invasion and metastasis are the hallmarks of malignant tumor progression and the main cause of death in cancer. The embryonic program "epithelial-mesenchymal transition" (EMT) is thought to trigger invasion by allowing tumor cell dissemination. Here, we describe that the EMT-inducing transcriptional repressor ZEB1 promotes colorectal cancer cell metastasis and loss of cell polarity. Thereby, ZEB1 suppresses the expression of cell polarity factors, in particular of Lgl2, which we found reduced in colorectal and breast cancers. We further show that retention of Lgl2 expression is critical for the epithelial phenotype and that its loss might be involved in metastasis. Thus, by linking EMT, loss of polarity, and metastasis, ZEB1 is a crucial promoter of malignant tumor progression.