A novel role of Keap1-Nrf2 signaling pathway underlying the regulation of cancer cells invasion.

Keap 1-Nrf 2是一个信号通路，强烈影响对氧化应激的内在抗性，并控制对各种环境应激的适应性反应。尽管Keap 1-Nrf 2通路的激活由于在正常细胞中诱导抗氧化剂和解毒酶而有助于癌症预防的策略，但Nrf 2激活也促进癌细胞的存活和发展。在目前的研究中，增加浓度的Nrf 2过表达导致ARE结合位点介导的MMP启动子活性显著增强。同样，我已经证明使用Keap 1的基因敲除技术，MMP基因在癌细胞中被显著诱导。这些结果表明，Keap 1-Nrf 2的激活不仅有助于癌细胞的发展，而且还促进了侵袭和转移。

Keap1-Nrf2 is a signaling pathway that strongly influences intrinsic resistant to oxidative stresses and controls adaptive responses to various environmental stressors. Whereas activation of Keap1-Nrf2 pathway contributes the strategy for cancer prevention due to induction of antioxidant and detoxication enzymes in normal cells, Nrf2 activation also promotes survival and development in cancer cells. In the current study, the overexpression of Nrf2 in increasing concentrations resulted in significant enhancement ARE binding sites-mediated MMP promoter activity. Similarly, I have demonstrated using gene knockdown technique of Keap1 that MMP gene was dramatically induced in cancer cells. These results suggested that the activation of Keap1-Nrf2 is not only contributed to cancer cells development but also promotes invasion and metastasis.