Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells

被引:10
作者
Hong, On-Yu [1 ]
Kang, Sang Yull [2 ,3 ]
Noh, Eun-Mi [1 ]
Yu, Hong-Nu [1 ]
Jang, Hye-Yeon [1 ]
Kim, Seong-Hun [4 ]
Hong, Jingyu [5 ]
Chung, Eun Yong [5 ]
Kim, Jong-Suk [1 ]
机构
[1] Jeonbuk Natl Univ, Inst Med Sci, Dept Biochem, Med Sch, Jeonju 54907, South Korea
[2] Jeonbuk Natl Univ, Dept Surg, Res Inst Clin Med, Jeonju 54907, South Korea
[3] Jeonbuk Natl Univ Hosp, Biomed Res Inst, Jeonju 54907, South Korea
[4] Jeonbuk Natl Univ, Res Inst Clin Med, Dept Internal Med, Div Gastroenterol,Med Sch & Hosp, Jeonju 54907, South Korea
[5] Catholic Univ Korea, Coll Med, Dept Anesthesiol & Pain Med, Bucheon St Marys Hosp, Seoul 06591, South Korea
基金
新加坡国家研究基金会;
关键词
Aurora kinase A; Colon cancer; Epithelia-to-mesenchymal transition; Matrix metalloproteinase-9; Protein kinase C; NF-KAPPA-B; MATRIX METALLOPROTEINASES; EXPRESSION; PROTEIN; TARGET; SNAIL; CHFR;
D O I
10.5483/BMBRep.2022.55.2.169
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 alpha-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. More-over, 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-kappa 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.
引用
收藏
页码:87 / 91
页数:5
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