title: Dose-dependent modulation of HIF-1alpha/sima controls the rate of cell migration and invasion in Drosophila ovary border cells.
abstract: The role of the hypoxic response during metastasis was analysed in migrating border cells of the Drosophila ovary. Acute exposure to 1% O(2) delayed or blocked border cell migration (BCM), whereas prolonged exposure resulted in the first documented accelerated BCM phenotype. Similarly, manipulating the expression levels of sima, the Drosophila hypoxia-inducible factor (HIF)-1alpha ortholog, revealed that Sima can either block or restore BCM in a dose-dependent manner. In contrast, over-expression of Vhl (Drosophila von Hippel-Lindau) generated a range of phenotypes, including blocked, delayed and accelerated BCM, whereas over-expression of hph (Drosophila HIF prolyl hydroxylase) only accelerated BCM. Mosaic clone analysis of sima or tango (HIF-1beta ortholog) mutants revealed that cells lacking Hif-1 transcriptional activity were preferentially detected in the leading cell position of the cluster, resulting in either a delay or acceleration of BCM. Moreover, in sima mutant cell clones, there was reduced expression of nuclear slow border cells (Slbo) and basolateral DE-cadherin, proteins essential for proper BCM. These results show that Sima levels define the rate of BCM in part through regulation of Slbo and DE-cadherin, and suggest that dynamic regulation of Hif-1 activity is necessary to maintain invasive potential of migrating epithelial cells.
authors: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. sdoronki@utmem.edu
authors: S
authors: S
authors: Doronkin
authors: I
authors: I
authors: Djagaeva
authors: M E
authors: ME
authors: Nagle
authors: L T
authors: LT
authors: Reiter
authors: T N
authors: TN
authors: Seagroves
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D010053:Ovary / Q000473:pathology*
chemical_list: D051793:Hypoxia-Inducible Factor 1