Integrin-linked kinase affects signaling pathways and migration in thyroid cancer cells and is a potential therapeutic target

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• 作者：Lawrence A. Shirley ; MD^a ; ^{lawrence.shirley@osumc.edu" class="auth_mail" title="E-mail the corresponding author} ; Samantha McCarty ; PhD^a ; Ming-Chen Yang ; PhD^b ; Motoyasu Saji ; MD ; PhD^c ; Xiaoli Zhang ; PhD^d ; John Phay ; MD^a ; Matthew D. Ringel ; MD^c ; Ching-Shih Chen ; PhD^b
• 刊名：Surgery
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：159
• 期：1
• 页码：163-171
• 全文大小：936 K

文摘

Integrin-linked kinase (ILK) is a serine-threonine kinase that regulates interactions between the cell and the extracellular matrix. In many cancers, overexpression of ILK leads to increased cell proliferation, motility, and invasion. We hypothesized that ILK functions as a regulator of viability and migration in thyroid cancer cells.

Methods

5">Eleven human thyroid cancer cell lines were screened for ILK protein expression. The cell lines with the greatest expression were treated with either ILK small interfering RNA (siRNA) or a novel ILK inhibitor, T315, and the effects were evaluated via Western blot and migration assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays were performed to assess cell viability.

Results

siRNA against ILK decreased phosphorylation of downstream effectors Akt and MLC, as well as decreased migration. Treatment with T315 showed a dose-related decrease in both Akt and MLC phosphorylation, as well as decreased migration. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assays showed T315 to have an half maximal inhibitory concentration of less than 1 μM in cell lines with high ILK expression.

Conclusion

5">ILK is expressed differentially in thyroid cancer cell lines. Both ILK siRNA and T315 inhibit motility of thyroid cancer cell lines, and T315 is shown to be cytotoxic at low concentrations. Altogether, our study suggests that ILK may represent an important kinase in aggressive thyroid cancers.