Regulation of epithelial-to-mesenchymal transition in hypoxia by the HIF-1α network

Epithelial-to-mesenchymal transition (EMT) plays a significant role in cancer metastasis. A series of models have focused on EMT regulation by TGF-beta network. However, how EMT is regulated under hypoxia is less understood. We developed a model of HIF-1 alpha network to explore the potential link between EMT and the network topology. Our results revealed that three positive feedback loops, composed of HIF-1 alpha and its three targets SNAIL, TWIST, and miR-210, should be sequentially activated to induce EMT under aggravating hypoxia. We suggested that the number of the positive feedback loops is critical for determining the number of stable states in EMT. Our work may advance the understanding of the significance of network topology in the regulation of EMT.

Automated summary

The study demonstrated that under aggravating hypoxia, the sequential activation of three positive feedback loops involving HIF-1 alpha and its targets SNAIL, TWIST, and miR-210 is crucial for inducing EMT. The number of positive feedback loops was found to be critical in determining the number of stable states in EMT regulation. This research highlights the significance of network topology in EMT regulation.