Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells
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Aurora kinase is a family of serine/threonine kinases intimatelyassociated with mitotic progression and the development ofhuman cancers. Studies have shown that aurora kinases areimportant for the protein kinase C (PKC)-induced invasion ofcolon cancer cells. Recent studies have shown that aurora kinaseA promotes distant metastasis by inducing epithelial-to-mesenchymaltransition (EMT) in colon cancer cells. However, the roleof aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A onPKC-induced cell invasion, migration, and EMT in human SW480colon 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 decreasingE-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 ofaurora kinase A blocked TPA-induced vimentin and MMP-9 expression,and decreased E-cadherin expression. Furthermore, theknockdown of aurora kinase A decreased the transcriptionalactivity of NF-κB and AP-1 in PKC-stimulated SW480 cells. Thesefindings indicate that aurora kinase A induces migration andinvasion by inducing EMT in SW480 colon cancer cells. To thebest of our knowledge, this is the first study that showed aurorakinase A is a key molecule in PKC-induced metastasis in coloncancer cells.
Abstract
Aurora kinase is a family of serine/threonine kinases intimatelyassociated with mitotic progression and the development ofhuman cancers. Studies have shown that aurora kinases areimportant for the protein kinase C (PKC)-induced invasion ofcolon cancer cells. Recent studies have shown that aurora kinaseA promotes distant metastasis by inducing epithelial-to-mesenchymaltransition (EMT) in colon cancer cells. However, the roleof aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A onPKC-induced cell invasion, migration, and EMT in human SW480colon 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 decreasingE-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 ofaurora kinase A blocked TPA-induced vimentin and MMP-9 expression,and decreased E-cadherin expression. Furthermore, theknockdown of aurora kinase A decreased the transcriptionalactivity of NF-κB and AP-1 in PKC-stimulated SW480 cells. Thesefindings indicate that aurora kinase A induces migration andinvasion by inducing EMT in SW480 colon cancer cells. To thebest of our knowledge, this is the first study that showed aurorakinase A is a key molecule in PKC-induced metastasis in coloncancer cells.
참고문헌 (27)
- Privette LM, "CHFR : a novel mitotic checkpoint protein and regulator of tumorigenesis", Transl Oncol, 1, pp.57~64 (2008)
- Carvajal RD, "Aurora kinases : new targets for cancer therapy", Clin Cancer Res, 12, pp.6869~6875 (2006)
- Yu X, "Chfr is required for tumor suppression and Aurora A regulation", Nat Genet, 37, pp.401~406 (2005)
- Tang A, "Aurora kinases : novel therapy targets in cancers", Oncotarget, 8, pp.23937~23954 (2017)
- Du R, "Targeting AURKA in cancer : molecular mechanisms and opportunities for cancer therapy", Mol Cancer, 20, pp.15~ (2021)
- Jemal A, "Global patterns of cancer incidence and mortality rates and trends", Cancer Epidemiol Biomarkers Prev, 19, pp.1893~1907 (2010)
- Siegel R, "Cancer statistics, 2013", CA Cancer J Clin, 63, pp.11~30 (2013)
- Mathias RA, "Contribution of cells undergoing epithelial-mesenchymal transition to the tumour microenvironment", J Proteomics, 78, pp.545~557 (2013)
- Thiery JP, "Complex networks orchestrate epithelial-mesenchymal transitions", Nat Rev Mol Cell Biol, 7, pp.131~142 (2006)
- Batlle E, "The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells", Nat Cell Biol, 2, pp.84~89 (2000)
- Usman S, "Vimentin is at the heart of epithelial mesenchymal transition(emt)mediated metastasis", Cancers(Basel), 13, pp.4985~ (2021)
- Parekh DB, "Multiple pathways control protein kinase C phosphorylation", EMBO J, 19, pp.496~503 (2000)
- Tarafdar A, "Protein kinase C in cellular transformation : a valid target for therapy?", Biochem Soc Trans, 42, pp.1556~1562 (2014)
- Masur K, "High PKC alpha and low E-cadherin expression contribute to high migratory activity of colon carcinoma cells", Mol Biol Cell, 12, pp.1973~1982 (2001)
- Noh EM, "Aurora kinases are essential for PKC-induced invasion and matrix metalloproteinase-9 expression in MCF-7breast cancer cells", Oncol Rep, 34, pp.803~810 (2015)
- Serova M, "Preclinical and clinical development of novel agents that target the protein kinase C family", Semin Oncol, 33, pp.466~478 (2006)
- Julien S, "Activation of NFkappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition", Oncogene, 26, pp.7445~7456 (2007)
- Nam EH, "Twist1and AP-1 cooperatively upregulate integrin alpha5 expression to induce invasion and the epithelial-mesenchymal transition", Carcinogenesis, 36, pp.327~337 (2015)
- D’Assoro AB, "Aurora-A kinase as a promising therapeutic target in cancer", Front Oncol, 5, pp.295~ (2015)
- D’Assoro, "The mitotic kinase Aurora-A promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERalpha(+)breast cancer cells", Oncogene, 33, pp.599~610 (2014)
- Goos JA, "Aurora kinase A(AURKA)expression in colorectal cancer liver metastasis is associated with poor prognosis", Br J Cancer, 109, pp.2445~2452 (2013)
- Steeghs N, "Phase I pharmacokinetic and pharmacodynamic study of the aurora kinase inhibitor danusertib in patients with advanced or metastatic solid tumors", J Clin Oncol, 27, pp.5094~5101 (2009)
- Bauvois B, "New facets of matrix metalloproteinases MMP-2 and MMP-9 as cell surface transducers : outside-in signaling and relationship to tumor progression", Biochim Biophys Acta, 1825, pp.29~36 (2012)
- Stetler-Stevenson WG, "Matrix metalloproteinases in angiogenesis : a moving target for therapeutic intervention", J Clin Invest, 103, pp.1237~1241 (1999)
- Nomura A, "Inhibition of NF-kappa B pathway leads to deregulation of epithelialmesenchymal transition and neural invasion in pancreatic cancer", Lab Invest, 96, pp.1268~1278 (2016)
- Julien S, "Activation of NFkappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition", Oncogene, 26, pp.7445~7456 (2007)
- Bakiri L, "Fra-1", AP-1induces EMT in mammary epithelial cells by modulating Zeb1, Cell Death Differ, pp.2015, 22[DOI]