Dose-dependent modulation of HIF-1α/ sima controls the rate of cell migration and invasion in Drosophila ovary border cells

摘要: The role of the hypoxic response during metastasis was analysed in migrating border cells Drosophila ovary. Acute exposure to 1% O2 delayed or blocked cell migration (BCM), whereas prolonged resulted first documented accelerated BCM phenotype. Similarly, manipulating expression levels sima, hypoxia-inducible factor (HIF)-1α ortholog, revealed that Sima can either block restore a dose-dependent manner. In contrast, over-expression Vhl (Drosophila von Hippel–Lindau) generated range phenotypes, including blocked, and BCM, hph HIF prolyl hydroxylase) only BCM. Mosaic clone analysis sima tango (HIF-1β ortholog) mutants lacking Hif-1 transcriptional activity were preferentially detected leading position cluster, resulting delay acceleration Moreover, mutant clones, there reduced nuclear slow (Slbo) basolateral DE-cadherin, proteins essential for proper These results show define rate part through regulation Slbo suggest dynamic is necessary maintain invasive potential epithelial cells.