Document Detail

Identification of DH IC-2 as a HIF-1 independent protein involved in the adaptive response to hypoxia in tumor cells: A putative role in metastasis.
MedLine Citation:
PMID:  19744529     Owner:  NLM     Status:  MEDLINE    
The master regulator of the adaptive response to hypoxia is HIF-1. However, while some data show that HIF-1 can control more than 80% of the genes induced under hypoxia, other experiments clearly demonstrate that a part of the hypoxic response is independent of HIF-1. The goal of this study was to identify some of these HIF-1 independent factors and to investigate their functional role in the adaptation of tumor cells to hypoxia. We show that the cytoplasmic dynein intermediate chain 2 (DH IC-2), a component of an intracellular ATPase minus-end directed tubulin-based motile complex, was stabilized and post-translationally modified under hypoxia in a HIF-1 independent way. We identified this modification as a phosphorylation by protein kinase C, which is inhibited under hypoxia. In parallel, the migration of HepG2 cells was enhanced under hypoxia. Cell migration was also increased, to the same extent, by the invalidation of DH IC-2 using siRNA. Taken together, these results suggest that under hypoxia, a specific modification of DH IC-2 may modulate its activity, and in turn promote cell migration. These results are important to better understand cancer development since they highlight a HIF-1 independent mechanism, which may be involved in metastasis.
Sebastien Pyr dit Ruys; Edouard Delaive; Catherine Demazy; Marc Dieu; Martine Raes; Carine Michiels
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-08
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1793     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-20     Completed Date:  2009-12-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1676-90     Citation Subset:  IM    
URBC, University of Namur-FUNDP, B-5000 Namur, Belgium.
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MeSH Terms
Carcinoma, Hepatocellular / metabolism*,  pathology
Cell Hypoxia
Cell Movement
Dyneins / antagonists & inhibitors,  metabolism*
Hep G2 Cells
Hypoxia-Inducible Factor 1*
Liver Neoplasms / metabolism*
Multiprotein Complexes / metabolism
Neoplasm Metastasis
Neoplasm Proteins / metabolism*
Protein Kinase C / metabolism
RNA, Small Interfering
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1; 0/Multiprotein Complexes; 0/Neoplasm Proteins; 0/RNA, Small Interfering; EC Kinase C; EC

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