Document Detail


Silencing of diphthamide synthesis 3 (Dph3) reduces metastasis of murine melanoma.
MedLine Citation:
PMID:  23185508     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Melanoma is the most dangerous skin cancer due to its highly metastatic potential and resistance to chemotherapy. Currently, there is no effective treatment for melanoma once it is progressed to metastatic stage. Therefore, further study to elucidate the molecular mechanism underlying the metastasis of melanoma cells is urgently required for the improvement of melanoma treatment. In the present study, we found that diphthamide synthesis 3 (Dph3) is involved in the metastasis of B16F10 murine melanoma cells by insertional mutagenesis. We demonstrated that Dph3 disruption impairs the migration of B16F10 murine melanoma cells. The requirement of Dph3 in the migration of melanoma cells was further confirmed by gene silencing with siRNA in vitro. In corresponding to this result, overexpression of Dph3 significantly promoted the migratory ability of B16F10 and B16F0 melanoma cells. Moreover, down regulation of Dph3 expression in B16F10 melanoma cells strikingly inhibits their cellular invasion and metastasis in vivo. Finally, we found that Dph3 promotes melanoma migration and invasion through the AKT signaling pathway. To conclude, our findings suggest a novel mechanism underlying the metastasis of melanoma cells which might serve as a new intervention target for the treatment of melanoma.
Authors:
Lei Wang; Yu Shi; Peijun Ju; Rui Liu; Siok Ping Yeo; Yinyan Xia; Hamed Owlanj; Zhiwei Feng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-20
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-11-27     Completed Date:  2013-05-30     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e49988     Citation Subset:  IM    
Affiliation:
School of Biological Sciences, Nanyang Technological University, Singapore, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carrier Proteins / genetics*,  metabolism
Cell Movement / genetics*
Gene Expression Regulation, Neoplastic
Gene Silencing*
Humans
Melanoma, Experimental* / enzymology,  genetics,  pathology
Mice
Neoplasm Invasiveness / genetics,  pathology
Neoplasm Metastasis / genetics,  pathology
Proto-Oncogene Proteins c-akt
RNA, Small Interfering / genetics,  metabolism
Sequence Homology, Amino Acid
Signal Transduction
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/DPH3 protein, human; 0/Dph3 protein, mouse; 0/RNA, Small Interfering; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
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