TIS21/BTG2 inhibits invadopodia formation by downregulating reactive oxygen species level in MDA-MB-231 cells.

Abstract

PURPOSE: Invasion of cancer cells depends on the proteolytic degradation of extracellular matrix regulated by actin-driven membrane protrusions, called invadopodia. However, the mechanisms underlying invadopodia formation in cancer cells remain largely unknown.

METHODS: By employing adenoviral transduction of breast cancer cells with either β-galactosidase (Ad-LacZ) or TIS21(/BTG2/Pc3) (Ad-TIS21) gene, the regulation of invadopodia formation was investigated. Invasion activity was examined by invadopodia assay and Matrigel assay. Intracellular reactive oxygen species (ROS) was monitored by FACS-based analysis.

RESULTS: Here, we observed that TIS21 suppressed invadopodia formation as well as invasion activity along with F-actin remodeling. The inhibition of TIS21-mediated invadopodia formation was accompanied with attenuation of ROS generation in the TIS21 expressers, indicating that TIS21-mediated inhibition of ROS plays a critical role for invadopodia formation by regulating actin-associated protein remodeling. This was further confirmed in the TIS21(-/-)MEF cells.

CONCLUSIONS: This is the first report to provide insight into invasion signals regulated by tumor suppressor, TIS21(/BTG2/Pc3) gene, in the intractable breast cancer cells.