The effect of Aurora kinases on cell proliferation, cell cycle regulation and metastasis in renal cell carcinoma
The effect of Aurora kinases on cell proliferation, cell cycle regulation and metastasis in renal cell carcinoma
复制标题
极光激酶对肾细胞癌细胞增殖、细胞周期调节和转移的影响。
DOI：
10.3892/ijo.2012.1633
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发表时间：
2012-12-01
影响因子：
5.2
通讯作者：
Chen, Xiaoguang
中科院分区：
文献类型：
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作者：
Li, Yan;Zhou, Wanqi;Chen, Xiaoguang
极光激酶已被证明参与细胞周期的调节，并与肿瘤进展有关。这表明它们可以作为肿瘤治疗的新抗癌靶点。然而，极光激酶及其信号通路在肾细胞癌（RCC）中发挥的重要作用尚未完全理解和解决。在这项研究中，我们旨在解决这些问题。我们观察到AurA miRNA、AurB miRNA或VX 680诱导的Aurora激酶的下调可以抑制透明细胞肾细胞癌细胞的增殖和转移，诱导G2/M期阻滞，并在SN 12 C异种移植模型中发挥抗肿瘤活性。我们还发现，Aurora激酶的沉默或VX 680处理细胞可通过阻断ERK活性下调cdc 25 c和cyclin B/cdc 2的表达，上调p-cdc 2（Tyr 15）的表达。这些变化可能与ccRCC的增殖抑制、转移和G2/M期阻滞有关。总之，我们证明极光激酶A和B都是肿瘤生长调节的关键要素，抑制极光激酶可能有助于阻断ccRCC进展。我们的结论是极光激酶可能是潜在的治疗目标在肾细胞癌的管理。
Aurora kinases have been shown to be involved in the regulation of the cell cycle and are related to tumor progression. This suggests the possibility that they can serve as new anticancer targets for tumor treatment. However, the important roles that Aurora kinases and their signaling pathway play in renal cell carcinoma (RCC) are not fully understood and addressed to date. In this study, we aimed to address these questions. We observed that downregulation of Aurora kinases induced by AurA miRNA, AurB miRNA or VX680 could inhibit proliferation and metastasis, induce G2/M phase arrest in clear cell renal cell carcinoma cells and exert antitumor activity in an SN12C xenograft model. We also show that either silencing of Aurora kinases or treating the cells with VX680 could downregulate the expression of cdc25c and cyclin B/cdc2, upregulate the expression of p-cdc2 (Tyr15) via blocking the activity of ERK. All these changes may contribute to inhibition of proliferation, metastasis and G2/M arrest in ccRCC. In summary, we proved that both Aurora kinases A and B are key elements of tumor growth regulation, and inhibition of Aurora kinases may contribute to blocking ccRCC progression. We conclude that Aurora kinases could be potential therapeutic targets in the management of renal cell carcinoma.