Document Detail


Dose-dependent modulation of HIF-1alpha/sima controls the rate of cell migration and invasion in Drosophila ovary border cells.
MedLine Citation:
PMID:  19966858     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
S Doronkin; I Djagaeva; M E Nagle; L T Reiter; T N Seagroves
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-12-07
Journal Detail:
Title:  Oncogene     Volume:  29     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-25     Completed Date:  2010-04-23     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  1123-34     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Hypoxia / physiology*
Cell Movement / physiology*
Dose-Response Relationship, Drug
Drosophila / cytology*,  genetics,  physiology
Female
Gene Expression Regulation, Neoplastic
Hypoxia-Inducible Factor 1 / physiology*
Neoplasm Invasiveness / physiopathology
Ovary / pathology*
Chemical
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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