NG2-mediated Rho activation promotes amoeboid invasiveness of cancer cells.

Abstract

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.

• Authors: Daniela Paňková, Njainday Jobe, Magdalena Kratochvílová, Roberto Buccione, Jan Brábek, Daniel Rösel
• Journal: European journal of cell biology (Eur J Cell Biol) 2012 Nov-Dec Vol. 91 Issue 11-12 Pg. 969-77 ISSN: 1618-1298 [Electronic] Germany
• PMID: 22699001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier GmbH. All rights reserved.

Chemical References

• CSPG4 protein, human
• Chondroitin Sulfate Proteoglycans
• Membrane Proteins
• RNA, Small Interfering
• Collagen
• rho-Associated Kinases
• rho GTP-Binding Proteins

Topics

• Animals
• Cell Line, Tumor
• Cell Movement
• Chondroitin Sulfate Proteoglycans (genetics, metabolism)
• Collagen (chemistry)
• Down-Regulation
• Extracellular Matrix (metabolism)
• Humans
• Membrane Proteins (genetics, metabolism)
• Molecular Conformation
• Neoplasm Invasiveness
• Neoplasms (metabolism, pathology, ultrastructure)
• RNA, Small Interfering
• Rats
• Up-Regulation
• rho GTP-Binding Proteins (metabolism)
• rho-Associated Kinases (metabolism)