Zhao Tangliang, Bao Yi, Lu Xin, He Yi, Gan Xinxin, Wang Jianchao, Liu Bing, Wang Linhui
Department of Urology, Changzheng Hospital, The Second Military Medical University, Shanghai 200001, P.R. China.
Department of Urology, Changhai Hospital, The Second Military Medical University, Shanghai 200003, P.R. China.
Oncol Lett. 2018 Nov;16(5):5953-5959. doi: 10.3892/ol.2018.9412. Epub 2018 Sep 6.
Proline-rich tyrosine kinase 2 (Pyk2), a member of the focal adhesion kinase family, has recently been associated with tumor development. However, the role of Pyk2 in renal cell carcinoma (RCC) remains unexplored. The present study investigated the expression pattern, clinical significance, and function of Pyk2 in RCC. By using a reverse transcription-quantitative polymerase chain reaction, tissue microarray and immunohistochemistry, it was demonstrated that RCC tissues display a higher Pyk2 expression compared with paired adjacent nontumor tissues. Furthermore, it was revealed that Pyk2 upregulation was associated with poor clinical outcomes in patients with RCC. By using loss-of-function approaches, it was demonstrated that Pyk2 knockdown reduced cell viability, invasive ability and migratory ability, and increased apoptosis in RCC cell lines. In contrast, Pyk2 overexpression promoted tumor cell proliferation, invasion and migration and reduced apoptosis. Collectively, the results of the present study present the tumor-promoting function of Pyk2 in RCC and thus provide molecular evidence for novel tyrosine kinase inhibitors as novel therapeutic options for RCC.
富含脯氨酸的酪氨酸激酶2（Pyk2）是粘着斑激酶家族的成员，最近被认为与肿瘤发展有关。然而，Pyk2在肾细胞癌（RCC）中的作用仍未被探索。本研究调查了Pyk2在RCC中的表达模式、临床意义及功能。通过逆转录定量聚合酶链反应、组织芯片和免疫组化分析，结果显示，与配对的相邻非肿瘤组织相比，RCC组织中Pyk2的表达更高。此外，研究还发现Pyk2的上调与RCC患者的不良临床预后相关。通过功能缺失实验表明，敲低Pyk2可降低RCC细胞系的细胞活力、侵袭能力和迁移能力，并增加细胞凋亡。相反，过表达Pyk2可促进肿瘤细胞增殖、侵袭和迁移，并减少细胞凋亡。总的来说，本研究结果揭示了Pyk2在RCC中的促肿瘤功能，从而为新型酪氨酸激酶抑制剂作为RCC的新型治疗选择提供了分子证据。
