Focal adhesion kinase overexpression and its impact on human osteosarcoma
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Ke Ren1,5,*, Xiao Lu2,*, Nan Yao3,*, Yong Chen4, Aizhen Yang2, Hui Chen5, Jian Zhang3, Sujia Wu4, Xin Shi4, Chen Wang5, Xiaoliang Sun1
1Department of Orthopedics, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Changzhou 213003, Jiangsu Province, P.R.China
2Center Laboratory of Cancer Center, The Jingdu hospital of Nanjing, Nanjing 210002, Jiangsu Province, P.R.China
3Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China
4Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, Jiangsu Province, P.R.China
5Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, P.R.China
*These authors have contributed equally to this work
Chen Wang, e-mail: firstname.lastname@example.org
Xiaoliang Sun, e-mail: email@example.com
Keywords: osteosarcoma, focal adhesion kinase, prognosis, migration, invasion
Received: November 01, 2014 Accepted: August 24, 2015 Published: September 03, 2015
Focal adhesion kinase (FAK) has been implicated in tumorigenesis in various malignancies. We sought to examine the expression patterns of FAK and the activated form, phosphorylated FAK (pFAK), in human osteosarcoma and to investigate the correlation of FAK expression with clinicopathologic parameters and prognosis. In addition, the functional consequence of manipulating the FAK protein level was investigated in human osteosarcoma cell lines. Immunohistochemical staining was used to detect FAK and pFAK in pathologic archived materials from 113 patients with primary osteosarcoma. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognoses. The role of FAK in the cytological behavior of MG63 and 143B human osteosarcoma cell lines was studied via FAK protein knock down with siRNA. Cell proliferation, migration, invasiveness and apoptosis were assessed using the CCK8, Transwell and Annexin V/PI staining methods. Both FAK and pFAK were overexpressed in osteosarcoma. There were significant differences in overall survival between the FAK-/pFAK- and FAK+/pFAK- groups (P = 0.016), the FAK+/pFAK- and FAK+/pFAK+ groups (P = 0.012) and the FAK-/pFAK- and FAK+/pFAK+ groups (P < 0.001). There were similar differences in metastasis-free survival between groups. The Cox proportional hazards analysis showed that the FAK expression profile was an independent indicator of both overall and metastasis-free survival. siRNA-based knockdown of FAK not only dramatically reduced the migration and invasion of MG63 and 143B cells, but also had a distinct effect on osteosarcoma cell proliferation and apoptosis. These results collectively suggest that FAK overexpression and phosphorylation might predict more aggressive biologic behavior in osteosarcoma and may be an independent predictor of poor prognosis.
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