Document Detail


Involvement of the mRNA binding protein CRD-BP in the regulation of metastatic melanoma cell proliferation and invasion by hypoxia.
MedLine Citation:
PMID:  23038779     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously shown that the mRNA binding protein CRD-BP is overexpressed in human melanomas, where it promotes cell survival and resistance to chemotherapy. The present study investigates the role of hypoxia, a common characteristic of the tumor microenvironment, in the regulation of CRD-BP expression and melanoma cell responses. We found that hypoxia increases CRD-BP levels in metastatic melanoma cell lines but not in melanocytes or primary melanoma cells. Hypoxic stimulation transcriptionally regulates CRD-BP by facilitating the acetylation of histones within the CRD-BP gene and by modulating the extent of HIF1α binding to the CRD-BP promoter. Hypoxia significantly enhances the proliferative and invasive potential of metastatic melanoma cells but not that of normal or primary melanoma cells. Furthermore, inhibition of CRD-BP impairs the ability of metastatic cells to proliferate and invade in response to hypoxia. These findings identify CRD-BP as a novel effector of hypoxic responses that is relevant for the selection of metastatic cells. This work also describes a previously unknown role for CRD-BP in the regulation of melanoma cell invasion and highlights the importance of the hypoxic microenvironment in determining cell fate.
Authors:
Evisabel A Craig; Jonathan D Weber; Vladimir S Spiegelman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-10-04
Journal Detail:
Title:  Journal of cell science     Volume:  125     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-02-28     Completed Date:  2014-01-29     Revised Date:  2014-03-20    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  5950-4     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Hypoxia / physiology
Cell Line, Tumor
Cell Proliferation
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Melanoma / genetics,  metabolism*,  pathology
Mice
Neoplasm Invasiveness
Promoter Regions, Genetic
RNA, Messenger / genetics,  metabolism*
RNA-Binding Proteins / genetics,  metabolism*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
AR055893/AR/NIAMS NIH HHS; AR063361/AR/NIAMS NIH HHS; CA121851/CA/NCI NIH HHS; P30 CA014520/CA/NCI NIH HHS; R01 AR063361/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/IMP-1 protein, human; 0/RNA, Messenger; 0/RNA-Binding Proteins
Comments/Corrections

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


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