Spaderna Simone, Schmalhofer Otto, Wahlbuhl Mandy, Dimmler Arno, Bauer Katja, Sultan Aneesa, Hlubek Falk, Jung Andreas, Strand Dennis, Eger Andreas, Kirchner Thomas, Behrens Jürgen, Brabletz Thomas
Department of Visceral Surgery, University of Freiburg, Freiburg, Germany.
Cancer Res. 2008 Jan 15;68(2):537-44. doi: 10.1158/0008-5472.CAN-07-5682.
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.
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。胚胎程序“上皮-间质转化”（EMT）被认为通过促进肿瘤细胞扩散来引发侵袭。在此，我们描述了诱导EMT的转录抑制因子ZEB1促进结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，我们发现其在结肠癌和乳腺癌中表达降低。我们进一步表明，Lgl2表达的保留对于上皮表型至关重要，其缺失可能与转移有关。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因子。
