title: Focal adhesion kinase overexpression and its impact on human osteosarcoma.
abstract: 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.
authors.affiliation: Department of Orthopedics, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Changzhou 213003, Jiangsu Province, P.R.China.|Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, P.R.China.
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.affiliation: Center Laboratory of Cancer Center, The Jingdu Hospital of Nanjing, Nanjing 210002, Jiangsu Province, P.R.China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yao
authors.affiliation: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, Jiangsu Province, P.R.China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Center Laboratory of Cancer Center, The Jingdu Hospital of Nanjing, Nanjing 210002, Jiangsu Province, P.R.China.
authors.forename: Aizhen
authors.initials: A
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, P.R.China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, Jiangsu Province, P.R.China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, Jiangsu Province, P.R.China.
authors.forename: Sujia
authors.initials: S
authors.lastname: Wu
authors.affiliation: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, Jiangsu Province, P.R.China.
authors.forename: Xin
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Orthopaedics, Zhongda Hospital, Southeast University, Nanjing 210009, Jiangsu Province, P.R.China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The Third Affiliated Hospital of Soochow University, The First People's Hospital of Changzhou, Changzhou 213003, Jiangsu Province, P.R.China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000201:enzymology / Q000473:pathology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D002648:Child; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000201:enzymology / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human
keywords: focal adhesion kinase; invasion; migration; osteosarcoma; prognosis