Activation of NF-κB by TOPK upregulates Snail/Slug expression in TGF-β1 signaling to induce epithelial-mesenchymal transition and invasion of breast cancer cells

Abstract

TGF-β1 is known to induce epithelial-mesenchymal transition (EMT), which is a prerequisite for cancer cell invasion. Here we reveal that TOPK upregulates EMT and invasion of human breast cancer MDA-MB-231 or Hs578T cells via NF-κB-dependent Snail/Slug in TGF-β1 signaling. Endogenous TOPK expression was significantly increased in response to TGF-β1 and TOPK knockdown mitigated TGF-β1-induced breast cancer cell invasion. Interestingly, TOPK knockdown restored TGF-β1 suppression of E-cadherin expression and markedly reduced N-cadherin induced by TGF-β1. Also, NF-κB activity or expression of EMT markers Snail and Slug induced by TGF-β1 was decreased by TOPK knockdown. Meanwhile, knockdown of Snail or TOPK attenuated TGF-β1-induced breast cancer cell invasion. Taken, we conclude that TOPK mediates TGF-β1-induced EMT and invasion in breast cancer cells via NF-κB/Snail signaling, suggesting novel role of TOPK as therapeutic target in TGF-β1-mediated breast cancer development.