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Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells
On-Yu Hong 1,# (Research worker), Sang Yull Kang2,# (Professor), Eun-Mi Noh1 (Research worker), Hong-Nu Yu1 (Research worker), Hye-Yeon Jang1 (Graduate student), Seong Hoon Kim3 (Professor), Jingyu Hong4 (Research worker), Eun Yong Chung4,# (Professor), Jong-Suk Kim 1,*,# (Professor)
1On-Yu Hong, Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School, Jeonju, Jeollabuk 54907,
2Sang Yull Kang, Department of Surgery, Research Institute of Clinical Medicine of Jeonbuk National University and Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Jeollabuk 54907,
3Eun-Mi Noh and 4Hong-Nu Yu and 5Hye-Yeon Jang, Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School, Jeonju, Jeollabuk 54907,
6Seong Hoon Kim, Division of Gastroenterology, Department of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School and Hospital, Jeonju, Jeonbuk 54907,
7Jingyu Hong and 8Eun Yong Chung, Department of Anesthesiology and Pain Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591,
9Jong-Suk Kim, Department of Biochemistry, Institute for Medical Sciences, Jeonbuk National University Medical School, Jeonju, Jeollabuk 54907
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 メ-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-リB 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.
Abstract, Accepted Manuscript(in press) [Submitted on November 24, 2021, Accepted on December 1, 2021]
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