Recombinant anthrax lethal toxin inhibits cell motility and invasion in breast cancer cells through the dysregulation of Rho GTPases

Breast cancer is the leading cause of cancer-associated death among women worldwide. Targeting breast cancer cell metastasis is an important therapeutic approach. The MAPK pathway is a key cell signaling pathway that plays a pivotal role in cellular invasion and migration. Numerous studies have identified the MAPK pathway as a way to target cell survival and motility. The present study treated MBA-MD-231 breast cancer cells with anthrax lethal toxin (LeTx), a potent MAPK inhibitor that selectively cleaves and inactivates all MEKs, as a potential therapeutic method to inhibit breast cancer cell migration. LeTx has been demonstrated to affect breast cancer cell migration. Cells treated with LeTx showed a significant decrease in motility, as observed using wound healing and random 2D motility assays. Additionally, cells treated with LeTx showed an increase in adhesion, which would explain the decrease in migration. Pull-down assays examining the activation status of the members of the Rho family of GTPases revealed an increase in RhoA activation accompanied by a decrease in Cdc42 activation following LeTx treatment. Finally, LeTx mediated a decrease in invasion using a Boyden chamber assay, which could be a result of the decrease in Cdc42 activation. The present study reported the effect of LeTx treatment on the migration, adhesion and invasion of breast cancer cells, demonstrating that this effect was associated with the dysregulation of the Rho GTPases, RhoA and Cdc42.