Department of Oromaxillofacial-Head and Neck Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, PR China.
Oncol Rep. 2012 Nov;28(5):1659-64. doi: 10.3892/or.2012.1989. Epub 2012 Aug 23.
Aberrant regulation in the chemotaxis and migration ability of cancer cells is closely associated with their metastatic activity. The chemokine receptor 7 (CCR7) has recently been shown to play an important role in regional lymph node metastasis of squamous cell carcinoma of the head and neck (SCCHN). In this study, we examined the role of proline-rich tyrosine kinase-2 (Pyk2) in CCR7-induced chemotaxis and migration ability of metastatic SCCHN cells. We showed that Pyk2 is overexpressed in squamous cell carcinoma of the head and neck. We also found that CCR7 induced Pyk2 and cofilin activation. Inhibition of Pyk2 activity using a pharmacological inhibitor, Tyrphostin A9, significantly attenuated CCR7-induced Pyk2 tyrosine phosphorylation, activation of cofilin and sequentially abolished F-actin rearrangment, diminished the chemotaxis and migration ability of SCCHN cells. In summary, our data suggest that CCR7 via Pyk2 and cofilin regulates the chemotaxis and migration ability of metastatic SCCHN cells.
癌细胞趋化性和迁移能力的异常调节与它们的转移活性密切相关。趋化因子受体 7（CCR7）最近被证明在头颈部鳞状细胞癌（SCCHN）的区域淋巴结转移中发挥重要作用。在这项研究中，我们研究了富含脯氨酸的酪氨酸激酶-2（Pyk2）在 CCR7 诱导的转移性 SCCHN 细胞趋化性和迁移能力中的作用。结果表明，Pyk2 在头颈部鳞状细胞癌中过表达。我们还发现 CCR7 诱导 Pyk2 和丝切蛋白 cofilin 的激活。使用药理学抑制剂 Tyrphostin A9 抑制 Pyk2 活性，可显著减弱 CCR7 诱导的 Pyk2 酪氨酸磷酸化、cofiln 的激活，继而破坏 F-肌动蛋白重排，降低 SCCHN 细胞的趋化性和迁移能力。综上所述，我们的数据表明 CCR7 通过 Pyk2 和丝切蛋白 cofilin 调节转移性 SCCHN 细胞的趋化性和迁移能力。
