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

Young-Ju Lee; Jung-Hwan Park; Sang-Muk Oh

doi:10.1016/j.bbrc.2019.11.104

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.

Authors

Young-Ju Lee¹, Jung-Hwan Park¹, Sang-Muk Oh²

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: sangmuk_oh@konyang.ac.kr.

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.

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

Substances

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