title: Aurora-A modulates MMP-2 expression via AKT/NF-κB pathway in esophageal squamous cell carcinoma cells.
abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies. It is necessary to identify new markers for predicting tumor progression and therapeutic molecular targets. It has been reported that overexpressions of Aurora-A and matrix metalloproteinases 2 (MMP-2) may promote the malignant development of tumor. However, the relationship between Aurora-A and MMP-2 expression in tumor patients has not been investigated. In addition, the underlying mechanisms that Aurora-A regulates MMP-2 expression are still not fully elucidated. In this study, we demonstrated that Aurora-A and MMP-2 were overexpressed in ESCC tissues compared with paired normal adjacent tissues (P < 0.0001). Overexpression of Aurora-A was associated with the lymph node metastasis of ESCC (P = 0.01). Significantly, Aurora-A protein expression was positively correlated with MMP-2 protein expression in ESCC tissues (r = 0.66, P < 0.0001) as well as in ESCC cell lines. The level of Aurora-A expression was also positively correlated with the invasion capability of ESCC cells. Furthermore, Aurora-A overexpression significantly increased ESCC cell invasion by the upregulation of MMP-2 expression. In addition, Aurora-A overexpression promoted nuclear factor-kappaB (NF-κB) activation, and Aurora-A-mediated MMP-2 upregulation was abrogated by NF-κB inhibitor. Further analysis showed that activation of NF-κB was severely attenuated by AKT inhibitor in cells overexpressing Aurora-A. Taken together, these data indicate that Aurora-A overexpression upregulates MMP-2 expression through activating AKT/NF-κB signaling pathway in ESCC cells. These findings reveal that Aurora-A may be used as an important indicator for the judgment of malignant behavior of ESCC, and may be an attractive target for cancer therapy.
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, No. 1 Hospital, Shanxi Medical University, Taiyuan 030001, China Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, China Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China wxiaoxia99007@126.com binquanwangsx@163.com.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Emergency, Shanxi Provincial People's Hospital, Taiyuan 030001, China.
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Chaohui
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Chun
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Benhong
authors.initials: B
authors.lastname: Ren
authors.affiliation: Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan 030001, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, No. 1 Hospital, Shanxi Medical University, Taiyuan 030001, China Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, No. 1 Hospital, Shanxi Medical University, Taiyuan 030001, China Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer, Taiyuan 030001, China wxiaoxia99007@126.com binquanwangsx@163.com.
authors.forename: Binquan
authors.initials: B
authors.lastname: Wang
mesh_terms: D064096:Aurora Kinase A / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; C576917:AURKA protein, human; D064096:Aurora Kinase A; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: Aurora-A; esophageal squamous cell carcinoma; matrix metalloproteinases 2; nuclear factor-κB