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.
Young-Ju Lee  1 ,  Jung-Hwan Park  1 ,  Sang-Muk Oh  2
Affiliations
  • 1. Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, South Korea.
  • 2. Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, South Korea; Priority Research Center, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, 35365, South Korea. Electronic address: [email protected].
PMID: 31757421 DOI: 10.1016/j.bbrc.2019.11.104
Abstract

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.
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