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

S. Doronkin, I. Djagaeva, M. E. Nagle, Lawrence Reiter, Tiffany Seagroves

Research output: Contribution to journalArticle

9 Citations (Scopus)

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)-1α 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-1Β 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.

Original languageEnglish (US)
Pages (from-to)1123-1134
Number of pages12
JournalOncogene
Volume29
Issue number8
DOIs
StatePublished - Feb 1 2010

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Hypoxia-Inducible Factor 1
Drosophila
Cell Movement
Ovary
Cadherins
Clone Cells
Prolyl Hydroxylases
Phenotype
Epithelial Cells
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Dose-dependent modulation of HIF-1α/sima controls the rate of cell migration and invasion in Drosophila ovary border cells. / Doronkin, S.; Djagaeva, I.; Nagle, M. E.; Reiter, Lawrence; Seagroves, Tiffany.

In: Oncogene, Vol. 29, No. 8, 01.02.2010, p. 1123-1134.

Research output: Contribution to journalArticle

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