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

Biochem Biophys Res Commun. 2020 Sep 10;530(1):122-129. doi: 10.1016/j.bbrc.2020.07.015. Epub 2020 Jul 30.

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.

Keywords: Epithelial-mesenchymal transition; Invasion; NF-κB; Snail; TGF-β1; TOPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology*
  • Signal Transduction
  • Snail Family Transcription Factors / genetics*
  • Transforming Growth Factor beta1 / metabolism*
  • Up-Regulation

Substances

  • NF-kappa B
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Mitogen-Activated Protein Kinase Kinases
  • PDZ-binding kinase