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Ou, Baochi; Zhao, Jingkun; Guan, Shaopei; Wangpu, Xiongzhi; Zhu, Congcong; Zong, Yaping; Ma, Junjun; Sun, Jing; Zheng, Minhua; Feng, Hao und Lu, Aiguo (2016): Plk2 promotes tumor growth and inhibits apoptosis by targeting Fbxw7/Cyclin E in colorectal cancer. In: Cancer Letters, Bd. 380, Nr. 2: S. 457-466

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Abstract

Polo-like kinase 2 (Plk2) and Polo-like kinase 3 (Plk3) have been documented as a tumor suppressor and are lowly expressed in several types of cancer. However, our results showed that Plk3 was lowly expressed, whereas Plk2 expressed highly in tumor tissues. We therefore aimed to explore the mechanisms governing the role of Plk2 in colorectal cancer (CRC). Our investigation demonstrated that Plk2 was an independent prognostic marker in CRC patients. Plk2 promotes tumor growth and inhibits apoptosis of CRC cells in vitro and in vivo. Moreover, Plk2 binds to Fbxw7 and results in its subsequent degradation, which,in turn leads to the stabilization of Cyclin E. The pro-tumor activity of Plk2 could be inverted by restoring Fbxw7 expression and depletion of Cyclin E. In addition, the expressions of Fbxw7 and Cyclin E were significantly associated with Plk2 protein levels in CRC tissues. In conclusion, our data show that Plk2 represents an independent prognostic marker and regulates tumor growth and apoptosis by targeting Fbxw7/Cyclin E pathway in CRC, suggesting Plk2 as a potential therapeutic target. (C) 2016 ELSEVIER. All rights reserved.

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