Different thresholds of ZEB1 are required for Ras-mediated tumour initiation and metastasis

作者：Liu Yongqing; Lu Xiaoqin; Huang Li; Wang Wei; Jiang Guomin; Dean Kevin C; Clem Brian; Telang Sucheta; Jenson Alfred B; Cuatrecasas Miriam; Chesney Jason; Darling Douglas S; Postigo Antonio^*; Dean Douglas C

来源：Nature Communications, 2014, 5(1): 5660.

DOI：10.1038/ncomms6660

Ras pathway mutation is frequent in carcinomas where it induces expression of the transcriptional repressor ZEB1. Although ZEB1 is classically linked to epithelial- mesenchymal transition and tumour metastasis, it has an emerging second role in generation of cancerinitiating cells. Here we show that Ras induction of ZEB1 is required for tumour initiation in a lung cancer model, and we link this function to repression Pten, whose loss is critical for emergence of cancer- initiating cells. These two roles for ZEB1 in tumour progression can be distinguished by their requirement for different levels of ZEB1. A lower threshold of ZEB1 is sufficient for cancer initiation, whereas further induction is necessary for tumour metastasis.

• 出版日期2014-12