title: Overexpression of Aurora-A enhances invasion and matrix metalloproteinase-2 expression in esophageal squamous cell carcinoma cells.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers, and metastasis is the principal cause of death in ESCC patients. It has been shown that amplification and overexpression of mitotic serine/threonine kinase Aurora-A occur in several types of human tumors, including ESCC. Moreover, increase in expression levels of Aurora-A has been predicted to correlate with the grades of tumor differentiation and invasive capability. However, the mechanisms by which Aurora-A mediates its invasive effects still remain elusive. In this article, we showed that Aurora-A overexpression significantly increased cell migration and invasion as well as secretion and expression of matrix metalloproteinase-2 (MMP-2). Conversely, siRNA-mediated knockdown of Aurora-A expression in human ESCC cells led to inhibition of cell invasiveness as well as secretion and expression of MMP-2. In addition, Aurora-A overexpression increased phosphorylation levels of p38 mitogen-activated protein kinase (MAPK) and Akt, and the knockdown of Aurora-A by siRNA decreased the activity of p38 MAPK and Akt. Moreover, the blocking of the activity of above kinases using chemical inhibitors suppressed the ability of Aurora-A to induce MMP-2 secretion and expression as well as cell invasion. These data show that overexpression of Aurora-A contributes to the malignancy development of ESCC by enhancing tumor cell invasion as well as MMP-2 activity and expression, which can occur through signaling pathways involving p38 MAPK and Akt protein kinases. Taken together, these studies provide a molecular basis for promoting the role of Aurora-A in malignancy development of ESCC.
authors.affiliation: Departments of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China. wxiaoxia99007@yahoo.com.cn
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Bo
authors.initials: B
authors.lastname: Niu
authors.forename: Xianjiu
authors.initials: X
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.forename: Niuliang
authors.initials: N
authors.lastname: Cheng
mesh_terms: D064127:Aurora Kinases; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering
chemical_list: D034741:RNA, Small Interfering; D064127:Aurora Kinases; D051058:Oncogene Protein v-akt; D017346:Protein Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020778:Matrix Metalloproteinase 2