Integrin-linked kinase is overexpressed in laryngeal squamous cell carcinoma and correlates with tumor proliferation, migration and invasion

P.-A. Wu, L.-L. Xie, D.-Y. Zhao, S.-S. Li, Q.-L. Tang, S.-H. Wang, X.-M. Yang

Department of Otolaryngology, Head and Neck Surgery, the University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, P.R. China. wupa@hku-szh.org

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• Oncology

OBJECTIVE: To investigate the role of integrin-linked kinase (ILK) in invasion and metastasis of the laryngeal squamous cell carcinomas (LSCC) and to evaluate the effects of antisense oligonucleotide sequence (ASONs) targeting the ILK gene on the proliferation, epithelial-mesenchymal transition (EMT), migration and invasion of LSCC.

PATIENTS AND METHODS: 116 patients who had previously undergone complete resection of the tumor for LSCC were studied retrospectively. The ILK expression level in tumor tissues and adjacent normal tissues were determined by immunohistochemistry. The changes of ILK expression from each group were assessed and correlated to the clinical parameters of the patients. Secondly, ILK antisense oligonucleotide (ILK-ASONS) was used to silence the ILK gene of LSCC cell from Hep-2 cell line. The expression of ILK, epithelial marker E-cadherin and mesenchymal marker Vimentin were evaluated by Western blotting. The proliferation of cells after transfection was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The apoptosis was detected by flow cytometry. The migration and invasion activity of Hep-2 cells was detected by Matrigel invasion and cell migration assays.

RESULTS: The expression of the ILK protein was significantly associated with tumor differentiation (p=0.046), lymph node metastasis (p=0.020) and pTNM stage (p=0.019). ILK ASONS-transfected cells showed a significant decrease in cell proliferation, cell migration and invasive activity compared to mock-transfected cells. ILK ASONS-transfected cells increased the expression of E-cadherin, whereas the expression of ILK and Vimentin decreased, compared with mock-transfected cells.

CONCLUSIONS: The expression of ILK was significantly correlated with differentiation and metastasis of the laryngeal carcinomas. The inhibition of the ILK gene could downregulate the proliferation, migration and invasion of Hep-2 cells. These findings suggest that the ILK gene could be a potential target for the treatment of laryngeal cancer.

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