Document Detail


Gadd45a inhibits cell migration and invasion by altering the global RNA expression.
MedLine Citation:
PMID:  22825327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gadd45a, the first well-defined p53 downstream gene, can be induced by multiple DNA-damaging agents, which plays important roles in the control of cell cycle checkpoint, DNA repair process and signaling transduction. Our previous findings suggested that Gadd45a maintains cell-cell adhesion and cell contact inhibition. However, little is known about how Gadd45a participates in the suppression of malignancy in human cancer cells. To examine the functions of Gadd45a in cell invasion and metastasis, we performed the adhesion, wound-healing and transwell assays in Gadd45a (+/+) and Gadd45a (-/-) MEF cell lines. We found the adhesion, migration and invasive abilities were much higher in Gadd45a deficient cells. We furthermore applied high-throughput cDNA microarray analysis and bioinformatics analysis to analyze the mechanisms of Gadd45a gene in invasion and metastasis. Compared with the Gadd45a wild type cells, the Gadd45a deficient cells showed a wide range of transcripts alterations. The altered gene pathways were predicted by the MAS software, which indicated focal adhesion,cell communication,ECM-receptor interaction as the three main pathways. Real-time PCR was employed to validate the differentially expressed genes. Interestingly, we figured out that the deregulations of these genes are caused neither by genomic aberrations nor methylation status. These findings provided a novel insight that Gadd45a may involve in tumor progression by regulating related genes expressions.
Authors:
Zhanhai Shan; Guiyuan Li; Qimin Zhan; Dan Li
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-07-24
Journal Detail:
Title:  Cancer biology & therapy     Volume:  13     ISSN:  1555-8576     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-12     Completed Date:  2013-04-11     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1112-22     Citation Subset:  IM    
Affiliation:
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Cell Adhesion / genetics
Cell Cycle Proteins / genetics*,  physiology
Cell Movement / genetics*
Gene Expression
Gene Silencing
Hep G2 Cells
Humans
Mice
Mice, Transgenic
Nuclear Proteins / genetics*,  physiology
RNA / biosynthesis*,  genetics
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/GADD45A protein, human; 0/Gadd45a protein, mouse; 0/Nuclear Proteins; 63231-63-0/RNA
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