Silencing of diphthamide synthesis 3 (Dph3) reduces metastasis of murine melanoma.

Abstract

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
• Journal: PloS one (PLoS One) Vol. 7 Issue 11 Pg. e49988 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23185508 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• DPH3 protein, human
• Dph3 protein, mouse
• Intracellular Signaling Peptides and Proteins
• RNA, Small Interfering
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Carrier Proteins (genetics, metabolism)
• Cell Movement (genetics)
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Humans
• Intracellular Signaling Peptides and Proteins
• 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