PTK2 Promotes Uveal Melanoma Metastasis by Activating Epithelial-to-Mesenchymal Transition

Abstract

Background: Uveal melanoma (UM) is an aggressive primary intraocular tumor in adults, with high metastatic capacity and high morbidity. However, the mechanisms of UM metastasis have not been clearly elucidated.Methods: The PTK2 expression and activation were performed in the Cancer Genome Atlas (TCGA) database and 25 patients of UM. The role of PTK2 in promoting metastasis was explored in vitro and in vivo. Subsequently, we revealed the correlation between PTK2 expression and epithelial-to-mesenchymal transition (EMT). Finally, we explored the reason for the high expression of PTK2 in UM.Results: Our study found that protein tyrosine kinase 2 (PTK2) was overexpressed in UM specimens, and as a novel independent risk factor, its overexpression predicted the poor survival of UM patients. For the molecular mechanism, PTK2 promoted EMT phenotype, thus leading to tumor metastasis in UM cells. Subsequently, we have demonstrated that PTK2 was a functional gene of chromosome 8q gain accounting for UM metastasis, providing a novel molecular mechanism for the aberrantly expression and activation of PTK2 in UM.Conclusion: Our data reveal the important role and mechanism of PTK2 in the metastatic process of UM, which may clue to a new predictive biomarker for UM metastasis and a new therapeutic target for UM treatment.