Biochemical and Biophysical Research Communications, Vol.530, No.1, 122-129, 2020
Activation of NF-kappa B by TOPK upregulates Snail/Slug expression in TGF-beta 1 signaling to induce epithelial-mesenchymal transition and invasion of breast cancer cells
TGF-beta 1 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-kappa B-dependent Snail/Slug in TGF-beta 1 signaling. Endogenous TOPK expression was significantly increased in response to TGF-beta 1 and TOPK knockdown mitigated TGF-beta 1-induced breast cancer cell invasion. Interestingly, TOPK knockdown restored TGF-beta 1 suppression of E-cadherin expression and markedly reduced N-cadherin induced by TGF-beta 1. Also, NF-kappa B activity or expression of EMT markers Snail and Slug induced by TGF-beta 1 was decreased by TOPK knockdown. Meanwhile, knockdown of Snail or TOPK attenuated TGF-beta 1-induced breast cancer cell invasion. Taken, we conclude that TOPK mediates TGF-beta 1-induced EMT and invasion in breast cancer cells via NF-kappa B/Snail signaling, suggesting novel role of TOPK as therapeutic target in TGF-beta 1-mediated breast cancer development. (C) 2020 Elsevier Inc. All rights reserved.