Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells Journal Article
| Authors: | Hamamura, K.; Furukawa, K.; Hayashi, T.; Hattori, T.; Nakano, J.; Nakashima, H.; Okuda, T.; Mizutani, H.; Hattori, H.; Ueda, M.; Urano, T.; Lloyd, K. O. |
| Article Title: | Ganglioside GD3 promotes cell growth and invasion through p130Cas and paxillin in malignant melanoma cells |
| Abstract: | Although ganglioside GD3 levels are highly elevated in malignant melanomas, the role of GD3 in melanomas' malignant properties has not been clearly shown. To investigate this problem, we genetically generated GD3-positive (GD3 +) transfectant cells from a GD3-negative (GD3 -) mutant line SK-MEL-28-N1 and analyzed the phenotypic changes in the transfected cells. GD3 + cells showed markedly increased cell growth and invasive characteristics. Two bands that underwent stronger tyrosine phosphorylation in GD3 + cell lines than in controls after treatment with FCS were found with molecular masses of 130 and 68 kDa. They were identified as p130Cas and paxillin by sequential immunoprecipitation. Their roles in cell growth and invasion were analyzed with a small interfering RNA (siRNA) approach. Cell growth, as analyzed by BrdUrd uptake, was strongly suppressed in GD3 + cells to near the levels of GD3 - cells when treated with siRNA for p130Cas but not when treated with siRNA for paxillin. However, treatment with siRNAs of either p130Cas or paxillin resulted in the marked suppression of the invasive activity of GD3 + cells almost to the levels of control cells. These results suggested that these two molecules function as effectors of GD3-mediated signaling, leading to such malignant properties as rapid cell growth and invasion. © 2005 by The National Academy of Sciences of the USA. |
| Keywords: | signal transduction; controlled study; protein phosphorylation; unclassified drug; human cell; proteins; phenotype; cell division; melanoma; cell growth; protein; small interfering rna; rna, small interfering; cancer cell culture; cell line, tumor; transfection; tyrosine; phosphorylation; cancer invasion; genetic transfection; sialyltransferase; sialyltransferases; immunoprecipitation; melanoma cell; phosphoproteins; neoplasm invasiveness; molecular weight; retinoblastoma-like protein p130; ganglioside gd3; crk associated substrate protein; crk-associated substrate protein; cytoskeletal proteins; gangliosides; paxillin |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 102 |
| Issue: | 31 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2005-08-02 |
| Start Page: | 11041 |
| End Page: | 11046 |
| Language: | English |
| DOI: | 10.1073/pnas.0503658102 |
| PUBMED: | 16040804 |
| PROVIDER: | scopus |
| PMCID: | PMC1180226 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 43" - "Export Date: 24 October 2012" - "CODEN: PNASA" - "Source: Scopus" |
