TOPK promotes epithelial-mesenchymal transition and invasion of breast cancer cells through upregulation of TBX3 in TGF-β1/Smad signaling

Biochem Biophys Res Commun. 2020 Jan 29;522(1):270-277. doi: 10.1016/j.bbrc.2019.11.104. Epub 2019 Nov 20.


TOPK has been suggested to contribute to invasion of lung, prostate, gastric, pancreatic or breast cancer cells. However, how TOPK mediates TGF-β1/Smad signaling leading to epithelial-mesenchymal transition (EMT) and invasion of breast cancer cells remains unknown. Here we report that TOPK upregulates T-box transcription factor TBX3 to enhance TGF-β1-induced EMT and invasion of MDA-MB-231 breast cancer cells. Expression of endogenous TOPK was promoted by TGF-β1 treatment of MDA-MB-231 cells time-dependently. In addition, knockdown of TOPK attenuated TGF-β1-induced phosphorylation or transcriptional activity of Smad3. Meanwhile, levels of both mRNA and protein of TBX3 induced by TGF-β1 were abolished by TOPK depletion. Also, knockdown of TBX3 inhibited TGF-β1 induction of EMT-related genes Snail, Slug or Fibronectin. Furthermore, ablation of TOPK or TBX3 suppressed TGF-β1-induced MDA-MB-231 cell invasion. Collectively, we conclude that TOPK positively regulates TBX3 in TGF-β1/Smad signaling pathway, thereby enhancing EMT and invasion of breast cancer cells, implying a mechanistic role of TOPK in TGF-β1/Smad signaling.

Keywords: Breast cancer; Epithelial-mesenchymal transition; Invasion; TBX3; TGF-β1; TOPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Signal Transduction
  • Smad Proteins / metabolism*
  • T-Box Domain Proteins / genetics*
  • T-Box Domain Proteins / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Up-Regulation


  • Smad Proteins
  • T-Box Domain Proteins
  • TBX3 protein, human
  • Transforming Growth Factor beta1
  • Mitogen-Activated Protein Kinase Kinases
  • PDZ-binding kinase