title: Plk2 promotes tumor growth and inhibits apoptosis by targeting Fbxw7/Cyclin E in colorectal cancer.
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.
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Baochi
authors.initials: B
authors.lastname: Ou
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jingkun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Shaopei
authors.initials: S
authors.lastname: Guan
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xiongzhi
authors.initials: X
authors.lastname: Wangpu
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zong
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Minhua
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Surgery, Hospital of the University of Munich, Munich, Germany. Electronic address: fenghaoobc@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: weichuang_lu@163.com.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Lu
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018938:Caco-2 Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D034622:RNA Interference; D015398:Signal Transduction; D016019:Survival Analysis; D013997:Time Factors; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019927:Cyclin E; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D044767:Ubiquitin-Protein Ligases; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Colorectal cancer; Cyclin E; Fbxw7; Plk2