Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

ZEB2 and Sp1 have cooperative roles as transcriptional activators of mesenchymal genes during EMT (#108)

Eun-Hee Nam 1 , Young-Kyu Park , Semi Kim 1
  1. Korea Research Institute of Bioscience and Biotechnology , Daejon , South Korea

Epithelial-mesenchymal transition (EMT) is a process implicated in tumor invasion, metastasis, embryonic development, and wound healing. ZEB2 is a transcription factor involved in EMT that represses E-cadherin transcription. Although E-cadherin downregulation is a major event during EMT and tumor progression, E-cadherin reduction is probably not sufficient for full invasiveness. The mechanisms by which E-cadherin transcriptional repressors induce mesenchymal genes during EMT remain largely unknown. Here, we investigated the role of ZEB2 in the induction of integrin α5 during cancer EMT and its underlying mechanism. In human cancer cells, ZEB2 was found to directly upregulate integrin α5 transcription in a manner that is independent of the regulation of E-cadherin expression. Conversely, depletion of ZEB2 by small interfering RNA suppressed integrin α5 expression, leading to reduced invasion. Suppression of integrin α5 inhibited cancer cell invasion, suggesting an important role for integrin α5 in cancer progression. Furthermore, ZEB2 was found to activate the integrin α5 and vimentin promoters by interacting with and activating the transcription factor Sp1, suggesting that cooperation between ZEB2 and Sp1 represents a novel mechanism of mesenchymal gene activation during EMT.