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-Amediated 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.

miR-145-5p Suppresses Tumor Cell Migration, Invasion and Epithelial to Mesenchymal Transition by Regulating the Sp1/NF-κB Signaling Pathway in Esophageal Squamous Cell Carcinoma

“…MMP2 , MMP7 and MMP13 , which were included in the family of matrix metalloproteinases (MMPs) were reported to play a central role in ESCC cell invasion and metastasis due to their ability to degrade the extracellular matrix [ 13 , 14 ]. Therefore, we detected whether miR-145-5p inhibited cell migration and invasion of ESCC cells via regulating these genes.…”

Identification of key genes and pathways for esophageal squamous cell carcinoma by bioinformatics analysis

“…CDK4/6 inhibitor-SHR6390 was reported to exert an antitumor effect against ESCC ( 43 ). AURKA, MCM7 and MCM4 were closely associated with cell proliferation and migration in ESCC ( 44 – 46 ). BUB1-related protein kinase was significantly higher in cancerous tissue than in adjacent normal tissue, and after radiochemotherapy, it was significantly decreased in the tissue of patients with ESCC ( 47 ).…”

Esophageal Cancer Development: Crucial Clues Arising from the Extracellular Matrix

“…Hence, because aberrant expression of MMP-2 and MMP-9 plays a key role along EC progression, different studies have shed some light on the mechanisms involved in the deregulation of MMP-2 and MMP-9 expression. Accordingly, the study published by Wang and colleagues revealed that overexpression of aurora A kinases (AURKA) in ESCC cell lines triggers a signaling pathway involving other kinases, such as p38 mitogen-activated protein kinases (p38) and protein kinase B (Akt), that culminates in MMP-2 expression and activity augmentation and, consequently, enhancement of ESCC cells' invasion abilities [80]. The involvement of the mitogen-activated protein kinase (MAPK) pathway seems to be a central mechanism in the regulation of MMP-2 and MMP-9 expression, as it it was demonstrated that a decrease in extracellular signal-regulated kinases (Erk) 1/2 and p38 phosphorylation, promoted by the tumor suppressor distinct subgroup of the Ras family member 1 (DIRAS1), leads to a down regulation of both MMPs [75].…”