title: CDK5 functions as a tumor promoter in human colorectal cancer via modulating the ERK5-AP-1 axis.
abstract: Abnormal expression of cyclin-dependent kinase 5 (CDK5) has been found in several human cancers, whereas the role of CDK5 in the malignant development of colorectal cancer (CRC) has not been well characterized. Here we investigated the role of CDK5 in CRC and found that its expression was much higher in CRC tissues than that in normal tissues with a higher expression level of CDK5 closely correlating to advanced American Joint Committee on Cancer (AJCC) stage, poor differentiation, increased tumor size and poor prognosis of CRC. Biological function experiments showed that CDK5 regulated CRC cell proliferation and metastasis ability. Whole-genome microarray analysis, co-immunoprecipitation, in vitro kinase assay, western blotting, luciferase reporter assays and electrophoretic mobility shift assay (EMSA) showed that CDK5 could directly phosphorylate ERK5 at threonine (Thr) 732 and finally modulate the oncogenic ERK5-AP-1 axis. Further researches showed that CDK5-ERK5-AP-1 axis could promote progression of CRC carcinogenesis and had a significant correlation in human CRC samples. In summary, this study revealed the functional and mechanistic links between CDK5 and the oncogenic ERK5-AP-1 signaling pathway in the pathogenesis of CRC. These findings suggest that CDK5 has an important role in CRC development and may serve as a potential therapeutic target for CRC.
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Kangmin
authors.initials: K
authors.lastname: Zhuang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Juchang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Man
authors.initials: M
authors.lastname: Xiong
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
authors.forename: Xianfei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Luo
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Liao
authors.affiliation: Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Side
authors.initials: S
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C500695:CDCA5 protein, human; D018797:Cell Cycle Proteins; D018808:Transcription Factor AP-1; D010769:Phosphothreonine; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7