Notch signaling mediates hypoxia-induced tumor cell migration and invasion

• DOI: 10.1073/pnas.0802047105
• Publication Date: 2008-04-22T05:23:47Z
• Authors: Cecilia Sahlgren; Maria V. Gustafsson; Shaobo Jin; Lorenz Poellinger; Urban Lendahl
• Keywords: Lysyl Oxidase; Hypoxia

Tumor hypoxia is linked to increased metastatic potential, but the molecular mechanisms coupling metastasis are poorly understood. Here, we show that Notch signaling required convert hypoxic stimulus into epithelial-mesenchymal transition (EMT), motility, and invasiveness. Inhibition of abrogated hypoxia-induced EMT invasion, and, conversely, an activated form could substitute for induce these processes. deploys two distinct act in synergy control expression Snail-1, a critical regulator EMT. First, directly up-regulated Snail-1 by recruitment intracellular domain promoter, second, potentiated hypoxia-inducible factor 1alpha (HIF-1alpha) lysyl oxidase (LOX) promoter elevated up-regulation LOX, which stabilizes protein. In sum, data demonstrate complex integration pathways regulation open up perspectives pharmacological intervention with hypoxiainduced cell invasiveness tumors.