NG2-mediated Rho activation promotes amoeboid invasiveness of cancer cells
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
22699001
DOI
10.1016/j.ejcb.2012.05.001
PII: S0171-9335(12)00083-0
Knihovny.cz E-resources
- MeSH
- Chondroitin Sulfate Proteoglycans genetics metabolism MeSH
- Down-Regulation MeSH
- Extracellular Matrix metabolism MeSH
- Neoplasm Invasiveness MeSH
- rho-Associated Kinases metabolism MeSH
- Collagen chemistry MeSH
- Rats MeSH
- Humans MeSH
- RNA, Small Interfering MeSH
- Membrane Proteins genetics metabolism MeSH
- Molecular Conformation MeSH
- Cell Line, Tumor MeSH
- Neoplasms metabolism pathology ultrastructure MeSH
- Cell Movement * MeSH
- rho GTP-Binding Proteins metabolism MeSH
- Up-Regulation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Chondroitin Sulfate Proteoglycans MeSH
- CSPG4 protein, human MeSH Browser
- rho-Associated Kinases MeSH
- Collagen MeSH
- RNA, Small Interfering MeSH
- Membrane Proteins MeSH
- rho GTP-Binding Proteins MeSH
The aim of this study was to analyze the potential role of NG2 chondroitin sulfate proteoglycan in amoeboid morphology and invasiveness of cancer cells. In the highly metastatic amoeboid cell lines A3 and A375M2, siRNA-mediated down-regulation of NG2 induced an amoeboid-mesenchymal transition associated with decreased invasiveness in 3D collagen and inactivation of the GTPase Rho. Conversely, the expression of NG2 in mesenchymal sarcoma K2 cells as well as in A375M2 cells resulted in an enhanced amoeboid phenotype associated with increased invasiveness and elevated Rho-GTP levels. Remarkably, the amoeboid-mesenchymal transition in A375M2 cells triggered by NG2 down-regulation was associated with increased extracellular matrix-degrading ability, although this was not sufficient to compensate for the decreased invasive capability caused by down-regulated Rho/ROCK signaling. Conversely, in K2 cells with overexpression of NG2, the ability to degrade the extracellular matrix was greatly reduced. Taken together, we suggest that NG2-mediated activation of Rho leading to effective amoeboid invasiveness is a possible mechanism through which NG2 could contribute to tumor cell invasion and metastasis.
References provided by Crossref.org
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