Affiliation:
1. Department of Bio‐Therapeutic Center and Oncology, Shenzhen Third People's Hospital Second Hospital Affiliated to Southern University of Science and Technology Shenzhen China
2. Tianjin Medical University Cancer Institute and Hospital Tianjin China
3. Department of Emergency Medicine, Shenzhen Third People's Hospital Second Hospital Affiliated to Southern University of Science and Technology Shenzhen China
4. Department of Oncology, The First Medical Centre Chinese PLA General Hospital Beijing China
Abstract
AbstractUveal melanoma (UM) is the most common primary intraocular malignant tumor in adults. More than half of UM cases develop distant metastasis to the liver, lung, bone, and other organs, which frequently results in patient death. However, the mechanisms underlying UM metastasis remain largely unknown. Here, we report that protein tyrosine kinase 2 (PTK2), a nonreceptor protein tyrosine kinase also known as focal adhesion kinase (FAK), was overexpressed in most examined UM specimens. Furthermore, we identified PTK2 expression as a novel independent risk factor that predicts poor prognosis of UM patients. Mechanistic studies revealed that PTK2 promotes the EMT phenotype, leading to metastasis of UM cells. We showed that PTK2, located on chromosome 8q, is a functional gene of chromosome 8q gain to UM metastasis, which may represent the molecular mechanism for the aberrant expression and activation of PTK2 in UM. Our data reveal a novel role and mechanism of PTK2 in the metastatic process of UM, suggesting PTK2 may be a potential prognostic biomarker for UM metastasis and a promising therapeutic target for UM treatment.
Funder
National Natural Science Foundation of China