Focal adhesion kinase overexpression and its impact on human osteosarcoma.
Focal adhesion kinase overexpression and its impact on human osteosarcoma.
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DOI：
10.18632/oncotarget.5044
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发表时间：
2015-10-13
期刊：
影响因子：
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通讯作者：
Sun X
中科院分区：
文献类型：
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作者：
Ren K;Lu X;Yao N;Chen Y;Yang A;Chen H;Zhang J;Wu S;Shi X;Wang C;Sun X
粘着斑激酶（FAK）与多种恶性肿瘤的发生有关。我们试图研究FAK和活化形式磷酸化FAK（pFAK）在人骨肉瘤中的表达模式，并研究FAK表达与临床病理参数和预后的相关性。此外，在人骨肉瘤细胞系中研究了操纵FAK蛋白水平的功能后果。应用免疫组织化学方法检测113例原发性骨肉瘤标本中FAK和pFAK的表达。采用Kaplan-Meier生存分析和考克斯回归分析评价生存率。通过siRNA干扰FAK蛋白表达，研究FAK在人骨肉瘤细胞系MG 63和143 B细胞中的细胞学行为。采用CCK 8、Transwell和Annexin V/PI染色法检测细胞增殖、迁移、侵袭和凋亡情况。FAK和pFAK在骨肉瘤中均过表达。FAK-/pFAK-组与FAK+/pFAK-组（P = 0.016）、FAK+/pFAK-组与FAK+/pFAK+组（P = 0.012）、FAK-/pFAK-组与FAK +/pFAK+组（P < 0.001）之间的总生存期有显著差异。两组间无转移生存率的差异相似。考克斯比例风险分析显示FAK表达谱是总生存期和无转移生存期的独立指标。siRNA敲低FAK不仅显著降低MG 63和143 B细胞的迁移和侵袭能力，而且对骨肉瘤细胞的增殖和凋亡有明显影响。这些结果共同表明，FAK过表达和磷酸化可能预示着骨肉瘤更具侵袭性的生物学行为，可能是预后不良的独立预测因子。
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.