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Abstract
Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors, and the main cause of death is metastasis. Overexpression of aurora kinaseA (AURKA) plays an important role in the metastasis of LSCC. However, the mechanism by which AURKA promotes the metastasis of LSCC is poorly understood. Recent accumulating evidence indicates that epithelial-mesenchymal transition (EMT) may be one of the mechanisms of tumor metastasis. In the present study, we studied whether AURKA may induce EMT to promote the metastasis of LSCC. CCK-8 and plate colony-formation assays were carried out to show that AURKA significantly promoted the proliferation of Hep2 cells. Immunofluorescence staining and western blotting showed that EMT-related proteins changed in a time-dependent manner along with the alteration of AURKA, with decreased expression of N-cadherin, vimentin and slug and increased expression of E-cadherin. Additionally, downregulation of the expression of AURKA inhibited FAK/PI3K pathway activity. Inhibition of the FAK/PI3K pathway caused less mesenchymal-like characteristics and reduced the mobility, migration and invasion of Hep2 cells. In conclusion, AURKA may induce EMT to promote metastasis via activation of the FAK/PI3K pathway in LSCC. Those regulatory factors may present new diagnostic biomarkers and potential therapeutic targets for LSCC.
Highlights
Laryngeal squamous cell carcinoma (LSCC), arises from the larynx epithelium and is one of the most common head and neck squamous cell carcinomas (HNSCCs) with a high rate of metastasis and a poor prognosis [1,2]
Our previous study showed that Aurora kinase A (AURKA) was yang et al: Activation of the FAK/PI3K pathway iN AURKA-induced epithelial-mesenchymal transition (EMT) in laryngeal cancer overexpressed in Hep2 cells and promoted the metastasis of LSCC [13,14]
Given that the FAK pathway is regarded as a regulatory factor in tumor metastasis [29,30,31] and FAK is involved in PI3K-promoted EMT in lung cancer [32], we aimed to demonstrate that AURKA regulates those factors to induce EMT
Summary
Laryngeal squamous cell carcinoma (LSCC), arises from the larynx epithelium and is one of the most common head and neck squamous cell carcinomas (HNSCCs) with a high rate of metastasis and a poor prognosis [1,2]. Recent treatment outcomes are improved, patients still have a poor prognosis with a 5-year survival rate of ~60% [5]. A better understanding of the underlying molecular metastasis-related mechanisms of LSCC is essential for developing effective therapeutic strategies to improve the survival rate and quality of life of these patients. It is an oncogene that causes various epithelial malignant tumors, including pancreatic [9], ovarian [10], colorectal [11] and prostate cancer [12]. The underlying mechanism by which AURKA enhances the metastasis of LSCC is still poorly understood
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