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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells

  • Hong, On-Yu (Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School) ;
  • Kang, Sang Yull (Department of Surgery, Research Institute of Clinical Medicine of Jeonbuk National University and Biomedical Research Institute of Jeonbuk National University Hospital) ;
  • Noh, Eun-Mi (Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School) ;
  • Yu, Hong-Nu (Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School) ;
  • Jang, Hye-Yeon (Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School) ;
  • Kim, Seong-Hun (Division of Gastroenterology, Department of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School and Hospital) ;
  • Hong, Jingyu (Department of Anesthesiology and Pain Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Chung, Eun Yong (Department of Anesthesiology and Pain Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Kim, Jong-Suk (Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School)
  • Received : 2021.11.24
  • Accepted : 2021.12.01
  • Published : 2022.02.28
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Abstract

Aurora kinase is a family of serine/threonine kinases intimately associated with mitotic progression and the development of human cancers. Studies have shown that aurora kinases are important for the protein kinase C (PKC)-induced invasion of colon cancer cells. Recent studies have shown that aurora kinase A promotes distant metastasis by inducing epithelial-to-mesenchymal transition (EMT) in colon cancer cells. However, the role of aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A on PKC-induced cell invasion, migration, and EMT in human SW480 colon cancer cells. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) changed the expression levels of EMT markers, increasing α-SMA, vimentin, and MMP-9 expression and decreasing E-cadherin expression, with changes in cell morphology. TPA treatment induced EMT in a PKC-dependent manner. Moreover, the inhibition of aurora kinase A by siRNAs and inhibitors (reversine and VX-680) suppressed TPA-induced cell invasion, migration, and EMT in SW480 human colon cells. Inhibition of aurora kinase A blocked TPA-induced vimentin and MMP-9 expression, and decreased E-cadherin expression. Furthermore, the knockdown of aurora kinase A decreased the transcriptional activity of NF-κB and AP-1 in PKC-stimulated SW480 cells. These findings indicate that aurora kinase A induces migration and invasion by inducing EMT in SW480 colon cancer cells. To the best of our knowledge, this is the first study that showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells.

Keywords

Acknowledgement

This study was supported by the Biomedical Research Institute, Jeonbuk National University Hospital, and the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2019R1A2C1003454 and 2020R1I1A1A01054100).

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