Plk2 promotes tumor growth and inhibits apoptosis by targeting Fbxw7/Cyclin E in colorectal cancer. Issue 2 (1st October 2016)

• Record Type: Journal Article
• Authors: Ou, Baochi; Zhao, Jingkun; Guan, Shaopei; Wangpu, Xiongzhi; Zhu, Congcong; Zong, Yaping; Ma, Junjun; Sun, Jing; Zheng, Minhua; Feng, Hao; Lu, Aiguo
• Is Part Of: Cancer letters. Volume 380:Issue 2(2016)
• Page Start: 457
• Page End: 466
• Publication Date: 2016-10-01
• Subjects: Colorectal cancer -- Plk2 -- Fbxw7 -- Cyclin E; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2016.07.004
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Plk3 was lowly expressed, whereas Plk2 was expressed highly in tumor tissues compared to paired normal tissues. Plk2 was previously reported as a tumor suppressor gene, while our findings suggest an oncogenic role for Plk2 in colorectal cancer. Plk2 represents an independent marker for predicting prognosis of colorectal cancer patients. Plk2 promotes tumor growth and inhibits apoptosis by targeting Fbxw7/Cyclin E pathway. 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.